ChloroquineV1, Pmc, Corpus, bibRecord, 000849

Autoantibody-Mediated Erythrophagocytosis Increases Tuberculosis Susceptibility in HIV Patients

Identifieur interne : 000849 ( Pmc/Corpus ); précédent : 000848; suivant : 000850

Autoantibody-Mediated Erythrophagocytosis Increases Tuberculosis Susceptibility in HIV Patients

Auteurs : Youchao Dai ; Yi Cai ; Xin Wang ; Jialou Zhu ; Xiaoqing Liu ; Houming Liu ; Linghua Li ; Yinze Zhang ; Shengze Liu ; Zhihua Wen ; Carl G. Feng ; Xinchun Chen ; Xiaoping Tang

Source :

mBio [ 2150-7511 ] ; 2020.

RBID : PMC:7042700

Abstract

HIV infection significantly increases TB susceptibility due to CD4 T-cell loss and macrophage dysfunction. Although it is relatively clear that CD4 T-cell loss represents a direct effect of HIV infection, the mechanism underlying how HIV infection dampens macrophage function is unknown. Here, we show that HIV infection enhances autoantibody-mediated erythrophagocytosis, which dampens macrophage bactericidal activity against TB by inhibiting HO-1-associated autophagy. Our findings reveal a novel mechanism explaining how HIV infection increases susceptibility to TB. We propose that DAT could be a potential measure to identify HIV patients who are at high TB risk and who would be suitable for anti-TB chemotherapy preventive treatment.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042700

DOI: 10.1128/mBio.03246-19
PubMed: 32098821
PubMed Central: 7042700

Links to Exploration step

PMC:7042700

Le document en format XML

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<author><name sortKey="Zhu, Jialou" sort="Zhu, Jialou" uniqKey="Zhu J" first="Jialou" last="Zhu">Jialou Zhu</name>
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<front><div type="abstract" xml:lang="en"><p>HIV infection significantly increases TB susceptibility due to CD4 T-cell loss and macrophage dysfunction. Although it is relatively clear that CD4 T-cell loss represents a direct effect of HIV infection, the mechanism underlying how HIV infection dampens macrophage function is unknown. Here, we show that HIV infection enhances autoantibody-mediated erythrophagocytosis, which dampens macrophage bactericidal activity against TB by inhibiting HO-1-associated autophagy. Our findings reveal a novel mechanism explaining how HIV infection increases susceptibility to TB. We propose that DAT could be a potential measure to identify HIV patients who are at high TB risk and who would be suitable for anti-TB chemotherapy preventive treatment.</p>
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<back><div1 type="bibliography"><listBibl><biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Bell, Lck" uniqKey="Bell L">LCK Bell</name>
</author>
<author><name sortKey="Noursadeghi, M" uniqKey="Noursadeghi M">M Noursadeghi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Getahun, H" uniqKey="Getahun H">H Getahun</name>
</author>
<author><name sortKey="Gunneberg, C" uniqKey="Gunneberg C">C Gunneberg</name>
</author>
<author><name sortKey="Granich, R" uniqKey="Granich R">R Granich</name>
</author>
<author><name sortKey="Nunn, P" uniqKey="Nunn P">P Nunn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sonnenberg, P" uniqKey="Sonnenberg P">P Sonnenberg</name>
</author>
<author><name sortKey="Glynn, Jr" uniqKey="Glynn J">JR Glynn</name>
</author>
<author><name sortKey="Fielding, K" uniqKey="Fielding K">K Fielding</name>
</author>
<author><name sortKey="Murray, J" uniqKey="Murray J">J Murray</name>
</author>
<author><name sortKey="Godfrey Faussett, P" uniqKey="Godfrey Faussett P">P Godfrey-Faussett</name>
</author>
<author><name sortKey="Shearer, S" uniqKey="Shearer S">S Shearer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kalsdorf, B" uniqKey="Kalsdorf B">B Kalsdorf</name>
</author>
<author><name sortKey="Scriba, Tj" uniqKey="Scriba T">TJ Scriba</name>
</author>
<author><name sortKey="Wood, K" uniqKey="Wood K">K Wood</name>
</author>
<author><name sortKey="Day, Cl" uniqKey="Day C">CL Day</name>
</author>
<author><name sortKey="Dheda, K" uniqKey="Dheda K">K Dheda</name>
</author>
<author><name sortKey="Dawson, R" uniqKey="Dawson R">R Dawson</name>
</author>
<author><name sortKey="Hanekom, Wa" uniqKey="Hanekom W">WA Hanekom</name>
</author>
<author><name sortKey="Lange, C" uniqKey="Lange C">C Lange</name>
</author>
<author><name sortKey="Wilkinson, Rj" uniqKey="Wilkinson R">RJ Wilkinson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Geldmacher, C" uniqKey="Geldmacher C">C Geldmacher</name>
</author>
<author><name sortKey="Ngwenyama, N" uniqKey="Ngwenyama N">N Ngwenyama</name>
</author>
<author><name sortKey="Schuetz, A" uniqKey="Schuetz A">A Schuetz</name>
</author>
<author><name sortKey="Petrovas, C" uniqKey="Petrovas C">C Petrovas</name>
</author>
<author><name sortKey="Reither, K" uniqKey="Reither K">K Reither</name>
</author>
<author><name sortKey="Heeregrave, Ej" uniqKey="Heeregrave E">EJ Heeregrave</name>
</author>
<author><name sortKey="Casazza, Jp" uniqKey="Casazza J">JP Casazza</name>
</author>
<author><name sortKey="Ambrozak, Dr" uniqKey="Ambrozak D">DR Ambrozak</name>
</author>
<author><name sortKey="Louder, M" uniqKey="Louder M">M Louder</name>
</author>
<author><name sortKey="Ampofo, W" uniqKey="Ampofo W">W Ampofo</name>
</author>
<author><name sortKey="Pollakis, G" uniqKey="Pollakis G">G Pollakis</name>
</author>
<author><name sortKey="Hill, B" uniqKey="Hill B">B Hill</name>
</author>
<author><name sortKey="Sanga, E" uniqKey="Sanga E">E Sanga</name>
</author>
<author><name sortKey="Saathoff, E" uniqKey="Saathoff E">E Saathoff</name>
</author>
<author><name sortKey="Maboko, L" uniqKey="Maboko L">L Maboko</name>
</author>
<author><name sortKey="Roederer, M" uniqKey="Roederer M">M Roederer</name>
</author>
<author><name sortKey="Paxton, Wa" uniqKey="Paxton W">WA Paxton</name>
</author>
<author><name sortKey="Hoelscher, M" uniqKey="Hoelscher M">M Hoelscher</name>
</author>
<author><name sortKey="Koup, Ra" uniqKey="Koup R">RA Koup</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bell, Lc" uniqKey="Bell L">LC Bell</name>
</author>
<author><name sortKey="Pollara, G" uniqKey="Pollara G">G Pollara</name>
</author>
<author><name sortKey="Pascoe, M" uniqKey="Pascoe M">M Pascoe</name>
</author>
<author><name sortKey="Tomlinson, Gs" uniqKey="Tomlinson G">GS Tomlinson</name>
</author>
<author><name sortKey="Lehloenya, Rj" uniqKey="Lehloenya R">RJ Lehloenya</name>
</author>
<author><name sortKey="Roe, J" uniqKey="Roe J">J Roe</name>
</author>
<author><name sortKey="Meldau, R" uniqKey="Meldau R">R Meldau</name>
</author>
<author><name sortKey="Miller, Rf" uniqKey="Miller R">RF Miller</name>
</author>
<author><name sortKey="Ramsay, A" uniqKey="Ramsay A">A Ramsay</name>
</author>
<author><name sortKey="Chain, Bm" uniqKey="Chain B">BM Chain</name>
</author>
<author><name sortKey="Dheda, K" uniqKey="Dheda K">K Dheda</name>
</author>
<author><name sortKey="Noursadeghi, M" uniqKey="Noursadeghi M">M Noursadeghi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Esmail, H" uniqKey="Esmail H">H Esmail</name>
</author>
<author><name sortKey="Riou, C" uniqKey="Riou C">C Riou</name>
</author>
<author><name sortKey="Bruyn, Ed" uniqKey="Bruyn E">ED Bruyn</name>
</author>
<author><name sortKey="Lai, Rp" uniqKey="Lai R">RP Lai</name>
</author>
<author><name sortKey="Harley, Yxr" uniqKey="Harley Y">YXR Harley</name>
</author>
<author><name sortKey="Meintjes, G" uniqKey="Meintjes G">G Meintjes</name>
</author>
<author><name sortKey="Wilkinson, Ka" uniqKey="Wilkinson K">KA Wilkinson</name>
</author>
<author><name sortKey="Wilkinson, Rj" uniqKey="Wilkinson R">RJ Wilkinson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gupta, A" uniqKey="Gupta A">A Gupta</name>
</author>
<author><name sortKey="Wood, R" uniqKey="Wood R">R Wood</name>
</author>
<author><name sortKey="Kaplan, R" uniqKey="Kaplan R">R Kaplan</name>
</author>
<author><name sortKey="Bekker, Lg" uniqKey="Bekker L">LG Bekker</name>
</author>
<author><name sortKey="Lawn, Sd" uniqKey="Lawn S">SD Lawn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jambo, Kc" uniqKey="Jambo K">KC Jambo</name>
</author>
<author><name sortKey="Banda, Dh" uniqKey="Banda D">DH Banda</name>
</author>
<author><name sortKey="Kankwatira, Am" uniqKey="Kankwatira A">AM Kankwatira</name>
</author>
<author><name sortKey="Sukumar, N" uniqKey="Sukumar N">N Sukumar</name>
</author>
<author><name sortKey="Allain, Tj" uniqKey="Allain T">TJ Allain</name>
</author>
<author><name sortKey="Heyderman, Rs" uniqKey="Heyderman R">RS Heyderman</name>
</author>
<author><name sortKey="Russell, Dg" uniqKey="Russell D">DG Russell</name>
</author>
<author><name sortKey="Mwandumba, Hc" uniqKey="Mwandumba H">HC Mwandumba</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mlcochova, P" uniqKey="Mlcochova P">P Mlcochova</name>
</author>
<author><name sortKey="Sutherland, Ka" uniqKey="Sutherland K">KA Sutherland</name>
</author>
<author><name sortKey="Watters, Sa" uniqKey="Watters S">SA Watters</name>
</author>
<author><name sortKey="Bertoli, C" uniqKey="Bertoli C">C Bertoli</name>
</author>
<author><name sortKey="De Bruin, Ra" uniqKey="De Bruin R">RA de Bruin</name>
</author>
<author><name sortKey="Rehwinkel, J" uniqKey="Rehwinkel J">J Rehwinkel</name>
</author>
<author><name sortKey="Neil, Sj" uniqKey="Neil S">SJ Neil</name>
</author>
<author><name sortKey="Lenzi, Gm" uniqKey="Lenzi G">GM Lenzi</name>
</author>
<author><name sortKey="Kim, B" uniqKey="Kim B">B Kim</name>
</author>
<author><name sortKey="Khwaja, A" uniqKey="Khwaja A">A Khwaja</name>
</author>
<author><name sortKey="Gage, Mc" uniqKey="Gage M">MC Gage</name>
</author>
<author><name sortKey="Georgiou, C" uniqKey="Georgiou C">C Georgiou</name>
</author>
<author><name sortKey="Chittka, A" uniqKey="Chittka A">A Chittka</name>
</author>
<author><name sortKey="Yona, S" uniqKey="Yona S">S Yona</name>
</author>
<author><name sortKey="Noursadeghi, M" uniqKey="Noursadeghi M">M Noursadeghi</name>
</author>
<author><name sortKey="Towers, Gj" uniqKey="Towers G">GJ Towers</name>
</author>
<author><name sortKey="Gupta, Rk" uniqKey="Gupta R">RK Gupta</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nunes Alves, C" uniqKey="Nunes Alves C">C Nunes-Alves</name>
</author>
<author><name sortKey="Booty, Mg" uniqKey="Booty M">MG Booty</name>
</author>
<author><name sortKey="Carpenter, Sm" uniqKey="Carpenter S">SM Carpenter</name>
</author>
<author><name sortKey="Jayaraman, P" uniqKey="Jayaraman P">P Jayaraman</name>
</author>
<author><name sortKey="Rothchild, Ac" uniqKey="Rothchild A">AC Rothchild</name>
</author>
<author><name sortKey="Behar, Sm" uniqKey="Behar S">SM Behar</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rothchild, Ac" uniqKey="Rothchild A">AC Rothchild</name>
</author>
<author><name sortKey="Sissons, Jr" uniqKey="Sissons J">JR Sissons</name>
</author>
<author><name sortKey="Shafiani, S" uniqKey="Shafiani S">S Shafiani</name>
</author>
<author><name sortKey="Plaisier, C" uniqKey="Plaisier C">C Plaisier</name>
</author>
<author><name sortKey="Min, D" uniqKey="Min D">D Min</name>
</author>
<author><name sortKey="Mai, D" uniqKey="Mai D">D Mai</name>
</author>
<author><name sortKey="Gilchrist, M" uniqKey="Gilchrist M">M Gilchrist</name>
</author>
<author><name sortKey="Peschon, J" uniqKey="Peschon J">J Peschon</name>
</author>
<author><name sortKey="Larson, Rp" uniqKey="Larson R">RP Larson</name>
</author>
<author><name sortKey="Bergthaler, A" uniqKey="Bergthaler A">A Bergthaler</name>
</author>
<author><name sortKey="Baliga, Ns" uniqKey="Baliga N">NS Baliga</name>
</author>
<author><name sortKey="Urdahl, Kb" uniqKey="Urdahl K">KB Urdahl</name>
</author>
<author><name sortKey="Aderem, A" uniqKey="Aderem A">A Aderem</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Martinez, V" uniqKey="Martinez V">V Martinez</name>
</author>
<author><name sortKey="Diemert, Mc" uniqKey="Diemert M">MC Diemert</name>
</author>
<author><name sortKey="Braibant, M" uniqKey="Braibant M">M Braibant</name>
</author>
<author><name sortKey="Potard, V" uniqKey="Potard V">V Potard</name>
</author>
<author><name sortKey="Charuel, Jl" uniqKey="Charuel J">JL Charuel</name>
</author>
<author><name sortKey="Barin, F" uniqKey="Barin F">F Barin</name>
</author>
<author><name sortKey="Costagliola, D" uniqKey="Costagliola D">D Costagliola</name>
</author>
<author><name sortKey="Caumes, E" uniqKey="Caumes E">E Caumes</name>
</author>
<author><name sortKey="Clauvel, Jp" uniqKey="Clauvel J">JP Clauvel</name>
</author>
<author><name sortKey="Autran, B" uniqKey="Autran B">B Autran</name>
</author>
<author><name sortKey="Musset, L" uniqKey="Musset L">L Musset</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="De Angelis, V" uniqKey="De Angelis V">V De Angelis</name>
</author>
<author><name sortKey="Biasinutto, C" uniqKey="Biasinutto C">C Biasinutto</name>
</author>
<author><name sortKey="Pradella, P" uniqKey="Pradella P">P Pradella</name>
</author>
<author><name sortKey="Vaccher, E" uniqKey="Vaccher E">E Vaccher</name>
</author>
<author><name sortKey="Spina, M" uniqKey="Spina M">M Spina</name>
</author>
<author><name sortKey="Tirelli, U" uniqKey="Tirelli U">U Tirelli</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lai, M" uniqKey="Lai M">M Lai</name>
</author>
<author><name sortKey="Visconti, E" uniqKey="Visconti E">E Visconti</name>
</author>
<author><name sortKey="D Onofrio, G" uniqKey="D Onofrio G">G D'Onofrio</name>
</author>
<author><name sortKey="Tamburrini, E" uniqKey="Tamburrini E">E Tamburrini</name>
</author>
<author><name sortKey="Cauda, R" uniqKey="Cauda R">R Cauda</name>
</author>
<author><name sortKey="Leone, G" uniqKey="Leone G">G Leone</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Silva Gomes, S" uniqKey="Silva Gomes S">S Silva-Gomes</name>
</author>
<author><name sortKey="Appelberg, R" uniqKey="Appelberg R">R Appelberg</name>
</author>
<author><name sortKey="Larsen, R" uniqKey="Larsen R">R Larsen</name>
</author>
<author><name sortKey="Soares, Mp" uniqKey="Soares M">MP Soares</name>
</author>
<author><name sortKey="Gomes, Ms" uniqKey="Gomes M">MS Gomes</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wagener, Bm" uniqKey="Wagener B">BM Wagener</name>
</author>
<author><name sortKey="Hu, Pj" uniqKey="Hu P">PJ Hu</name>
</author>
<author><name sortKey="Oh, Jy" uniqKey="Oh J">JY Oh</name>
</author>
<author><name sortKey="Evans, Ca" uniqKey="Evans C">CA Evans</name>
</author>
<author><name sortKey="Richter, Jr" uniqKey="Richter J">JR Richter</name>
</author>
<author><name sortKey="Honavar, J" uniqKey="Honavar J">J Honavar</name>
</author>
<author><name sortKey="Brandon, Ap" uniqKey="Brandon A">AP Brandon</name>
</author>
<author><name sortKey="Creighton, J" uniqKey="Creighton J">J Creighton</name>
</author>
<author><name sortKey="Stephens, Sw" uniqKey="Stephens S">SW Stephens</name>
</author>
<author><name sortKey="Morgan, C" uniqKey="Morgan C">C Morgan</name>
</author>
<author><name sortKey="Dull, Ro" uniqKey="Dull R">RO Dull</name>
</author>
<author><name sortKey="Marques, Mb" uniqKey="Marques M">MB Marques</name>
</author>
<author><name sortKey="Kerby, Jd" uniqKey="Kerby J">JD Kerby</name>
</author>
<author><name sortKey="Pittet, Jf" uniqKey="Pittet J">JF Pittet</name>
</author>
<author><name sortKey="Patel, Rp" uniqKey="Patel R">RP Patel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Meulenbroek, Em" uniqKey="Meulenbroek E">EM Meulenbroek</name>
</author>
<author><name sortKey="Wouters, D" uniqKey="Wouters D">D Wouters</name>
</author>
<author><name sortKey="Zeerleder, Ss" uniqKey="Zeerleder S">SS Zeerleder</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Parker, V" uniqKey="Parker V">V Parker</name>
</author>
<author><name sortKey="Tormey, Ca" uniqKey="Tormey C">CA Tormey</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kerkhoff, Ad" uniqKey="Kerkhoff A">AD Kerkhoff</name>
</author>
<author><name sortKey="Wood, R" uniqKey="Wood R">R Wood</name>
</author>
<author><name sortKey="Vogt, M" uniqKey="Vogt M">M Vogt</name>
</author>
<author><name sortKey="Lawn, Sd" uniqKey="Lawn S">SD Lawn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lai, M" uniqKey="Lai M">M Lai</name>
</author>
<author><name sortKey="D Onofrio, G" uniqKey="D Onofrio G">G d'Onofrio</name>
</author>
<author><name sortKey="Visconti, E" uniqKey="Visconti E">E Visconti</name>
</author>
<author><name sortKey="Tamburrini, E" uniqKey="Tamburrini E">E Tamburrini</name>
</author>
<author><name sortKey="Cauda, R" uniqKey="Cauda R">R Cauda</name>
</author>
<author><name sortKey="Leone, G" uniqKey="Leone G">G Leone</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Theurl, I" uniqKey="Theurl I">I Theurl</name>
</author>
<author><name sortKey="Hilgendorf, I" uniqKey="Hilgendorf I">I Hilgendorf</name>
</author>
<author><name sortKey="Nairz, M" uniqKey="Nairz M">M Nairz</name>
</author>
<author><name sortKey="Tymoszuk, P" uniqKey="Tymoszuk P">P Tymoszuk</name>
</author>
<author><name sortKey="Haschka, D" uniqKey="Haschka D">D Haschka</name>
</author>
<author><name sortKey="Asshoff, M" uniqKey="Asshoff M">M Asshoff</name>
</author>
<author><name sortKey="He, S" uniqKey="He S">S He</name>
</author>
<author><name sortKey="Gerhardt, Lm" uniqKey="Gerhardt L">LM Gerhardt</name>
</author>
<author><name sortKey="Holderried, Ta" uniqKey="Holderried T">TA Holderried</name>
</author>
<author><name sortKey="Seifert, M" uniqKey="Seifert M">M Seifert</name>
</author>
<author><name sortKey="Sopper, S" uniqKey="Sopper S">S Sopper</name>
</author>
<author><name sortKey="Fenn, Am" uniqKey="Fenn A">AM Fenn</name>
</author>
<author><name sortKey="Anzai, A" uniqKey="Anzai A">A Anzai</name>
</author>
<author><name sortKey="Rattik, S" uniqKey="Rattik S">S Rattik</name>
</author>
<author><name sortKey="Mcalpine, C" uniqKey="Mcalpine C">C McAlpine</name>
</author>
<author><name sortKey="Theurl, M" uniqKey="Theurl M">M Theurl</name>
</author>
<author><name sortKey="Wieghofer, P" uniqKey="Wieghofer P">P Wieghofer</name>
</author>
<author><name sortKey="Iwamoto, Y" uniqKey="Iwamoto Y">Y Iwamoto</name>
</author>
<author><name sortKey="Weber, Gf" uniqKey="Weber G">GF Weber</name>
</author>
<author><name sortKey="Harder, Nk" uniqKey="Harder N">NK Harder</name>
</author>
<author><name sortKey="Chousterman, Bg" uniqKey="Chousterman B">BG Chousterman</name>
</author>
<author><name sortKey="Arvedson, Tl" uniqKey="Arvedson T">TL Arvedson</name>
</author>
<author><name sortKey="Mckee, M" uniqKey="Mckee M">M McKee</name>
</author>
<author><name sortKey="Wang, F" uniqKey="Wang F">F Wang</name>
</author>
<author><name sortKey="Lutz, Om" uniqKey="Lutz O">OM Lutz</name>
</author>
<author><name sortKey="Rezoagli, E" uniqKey="Rezoagli E">E Rezoagli</name>
</author>
<author><name sortKey="Babitt, Jl" uniqKey="Babitt J">JL Babitt</name>
</author>
<author><name sortKey="Berra, L" uniqKey="Berra L">L Berra</name>
</author>
<author><name sortKey="Prinz, M" uniqKey="Prinz M">M Prinz</name>
</author>
<author><name sortKey="Nahrendorf, M" uniqKey="Nahrendorf M">M Nahrendorf</name>
</author>
<author><name sortKey="Weiss, G" uniqKey="Weiss G">G Weiss</name>
</author>
<author><name sortKey="Weissleder, R" uniqKey="Weissleder R">R Weissleder</name>
</author>
<author><name sortKey="Lin, Hy" uniqKey="Lin H">HY Lin</name>
</author>
<author><name sortKey="Swirski, Fk" uniqKey="Swirski F">FK Swirski</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Santarino, Ib" uniqKey="Santarino I">IB Santarino</name>
</author>
<author><name sortKey="Viegas, Ms" uniqKey="Viegas M">MS Viegas</name>
</author>
<author><name sortKey="Domingues, Ns" uniqKey="Domingues N">NS Domingues</name>
</author>
<author><name sortKey="Ribeiro, Am" uniqKey="Ribeiro A">AM Ribeiro</name>
</author>
<author><name sortKey="Soares, Mp" uniqKey="Soares M">MP Soares</name>
</author>
<author><name sortKey="Vieira, Ov" uniqKey="Vieira O">OV Vieira</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yang, R" uniqKey="Yang R">R Yang</name>
</author>
<author><name sortKey="Yang, E" uniqKey="Yang E">E Yang</name>
</author>
<author><name sortKey="Shen, L" uniqKey="Shen L">L Shen</name>
</author>
<author><name sortKey="Modlin, Rl" uniqKey="Modlin R">RL Modlin</name>
</author>
<author><name sortKey="Shen, H" uniqKey="Shen H">H Shen</name>
</author>
<author><name sortKey="Chen, Zw" uniqKey="Chen Z">ZW Chen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kimura, S" uniqKey="Kimura S">S Kimura</name>
</author>
<author><name sortKey="Noda, T" uniqKey="Noda T">T Noda</name>
</author>
<author><name sortKey="Yoshimori, T" uniqKey="Yoshimori T">T Yoshimori</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Singh, N" uniqKey="Singh N">N Singh</name>
</author>
<author><name sortKey="Kansal, P" uniqKey="Kansal P">P Kansal</name>
</author>
<author><name sortKey="Ahmad, Z" uniqKey="Ahmad Z">Z Ahmad</name>
</author>
<author><name sortKey="Baid, N" uniqKey="Baid N">N Baid</name>
</author>
<author><name sortKey="Kushwaha, H" uniqKey="Kushwaha H">H Kushwaha</name>
</author>
<author><name sortKey="Khatri, N" uniqKey="Khatri N">N Khatri</name>
</author>
<author><name sortKey="Kumar, A" uniqKey="Kumar A">A Kumar</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Castillo, Ef" uniqKey="Castillo E">EF Castillo</name>
</author>
<author><name sortKey="Dekonenko, A" uniqKey="Dekonenko A">A Dekonenko</name>
</author>
<author><name sortKey="Arko Mensah, J" uniqKey="Arko Mensah J">J Arko-Mensah</name>
</author>
<author><name sortKey="Mandell, Ma" uniqKey="Mandell M">MA Mandell</name>
</author>
<author><name sortKey="Dupont, N" uniqKey="Dupont N">N Dupont</name>
</author>
<author><name sortKey="Jiang, S" uniqKey="Jiang S">S Jiang</name>
</author>
<author><name sortKey="Delgado Vargas, M" uniqKey="Delgado Vargas M">M Delgado-Vargas</name>
</author>
<author><name sortKey="Timmins, Gs" uniqKey="Timmins G">GS Timmins</name>
</author>
<author><name sortKey="Bhattacharya, D" uniqKey="Bhattacharya D">D Bhattacharya</name>
</author>
<author><name sortKey="Yang, H" uniqKey="Yang H">H Yang</name>
</author>
<author><name sortKey="Hutt, J" uniqKey="Hutt J">J Hutt</name>
</author>
<author><name sortKey="Lyons, Cr" uniqKey="Lyons C">CR Lyons</name>
</author>
<author><name sortKey="Dobos, Km" uniqKey="Dobos K">KM Dobos</name>
</author>
<author><name sortKey="Deretic, V" uniqKey="Deretic V">V Deretic</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Martins, R" uniqKey="Martins R">R Martins</name>
</author>
<author><name sortKey="Knapp, S" uniqKey="Knapp S">S Knapp</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gozzelino, R" uniqKey="Gozzelino R">R Gozzelino</name>
</author>
<author><name sortKey="Jeney, V" uniqKey="Jeney V">V Jeney</name>
</author>
<author><name sortKey="Soares, Mp" uniqKey="Soares M">MP Soares</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bolisetty, S" uniqKey="Bolisetty S">S Bolisetty</name>
</author>
<author><name sortKey="Traylor, Am" uniqKey="Traylor A">AM Traylor</name>
</author>
<author><name sortKey="Kim, J" uniqKey="Kim J">J Kim</name>
</author>
<author><name sortKey="Joseph, R" uniqKey="Joseph R">R Joseph</name>
</author>
<author><name sortKey="Ricart, K" uniqKey="Ricart K">K Ricart</name>
</author>
<author><name sortKey="Landar, A" uniqKey="Landar A">A Landar</name>
</author>
<author><name sortKey="Agarwal, A" uniqKey="Agarwal A">A Agarwal</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name>
</author>
<author><name sortKey="Wang, Hx" uniqKey="Wang H">HX Wang</name>
</author>
<author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name>
</author>
<author><name sortKey="Huo, W" uniqKey="Huo W">W Huo</name>
</author>
<author><name sortKey="Li, Xd" uniqKey="Li X">XD Li</name>
</author>
<author><name sortKey="Qi, Rq" uniqKey="Qi R">RQ Qi</name>
</author>
<author><name sortKey="Song, Xy" uniqKey="Song X">XY Song</name>
</author>
<author><name sortKey="Wei, S" uniqKey="Wei S">S Wei</name>
</author>
<author><name sortKey="Gao, Xh" uniqKey="Gao X">XH Gao</name>
</author>
<author><name sortKey="Han, S" uniqKey="Han S">S Han</name>
</author>
<author><name sortKey="Cao, L" uniqKey="Cao L">L Cao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Keino, H" uniqKey="Keino H">H Keino</name>
</author>
<author><name sortKey="Nagae, H" uniqKey="Nagae H">H Nagae</name>
</author>
<author><name sortKey="Mimura, S" uniqKey="Mimura S">S Mimura</name>
</author>
<author><name sortKey="Watanabe, K" uniqKey="Watanabe K">K Watanabe</name>
</author>
<author><name sortKey="Kashiwamata, S" uniqKey="Kashiwamata S">S Kashiwamata</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Abdalla, My" uniqKey="Abdalla M">MY Abdalla</name>
</author>
<author><name sortKey="Ahmad, Im" uniqKey="Ahmad I">IM Ahmad</name>
</author>
<author><name sortKey="Switzer, B" uniqKey="Switzer B">B Switzer</name>
</author>
<author><name sortKey="Britigan, Be" uniqKey="Britigan B">BE Britigan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mitra, A" uniqKey="Mitra A">A Mitra</name>
</author>
<author><name sortKey="Speer, A" uniqKey="Speer A">A Speer</name>
</author>
<author><name sortKey="Lin, K" uniqKey="Lin K">K Lin</name>
</author>
<author><name sortKey="Ehrt, S" uniqKey="Ehrt S">S Ehrt</name>
</author>
<author><name sortKey="Niederweis, M" uniqKey="Niederweis M">M Niederweis</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mazzolini, J" uniqKey="Mazzolini J">J Mazzolini</name>
</author>
<author><name sortKey="Herit, F" uniqKey="Herit F">F Herit</name>
</author>
<author><name sortKey="Bouchet, J" uniqKey="Bouchet J">J Bouchet</name>
</author>
<author><name sortKey="Benmerah, A" uniqKey="Benmerah A">A Benmerah</name>
</author>
<author><name sortKey="Benichou, S" uniqKey="Benichou S">S Benichou</name>
</author>
<author><name sortKey="Niedergang, F" uniqKey="Niedergang F">F Niedergang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kyei, Gb" uniqKey="Kyei G">GB Kyei</name>
</author>
<author><name sortKey="Dinkins, C" uniqKey="Dinkins C">C Dinkins</name>
</author>
<author><name sortKey="Davis, As" uniqKey="Davis A">AS Davis</name>
</author>
<author><name sortKey="Roberts, E" uniqKey="Roberts E">E Roberts</name>
</author>
<author><name sortKey="Singh, Sb" uniqKey="Singh S">SB Singh</name>
</author>
<author><name sortKey="Dong, C" uniqKey="Dong C">C Dong</name>
</author>
<author><name sortKey="Wu, L" uniqKey="Wu L">L Wu</name>
</author>
<author><name sortKey="Kominami, E" uniqKey="Kominami E">E Kominami</name>
</author>
<author><name sortKey="Ueno, T" uniqKey="Ueno T">T Ueno</name>
</author>
<author><name sortKey="Yamamoto, A" uniqKey="Yamamoto A">A Yamamoto</name>
</author>
<author><name sortKey="Federico, M" uniqKey="Federico M">M Federico</name>
</author>
<author><name sortKey="Panganiban, A" uniqKey="Panganiban A">A Panganiban</name>
</author>
<author><name sortKey="Vergne, I" uniqKey="Vergne I">I Vergne</name>
</author>
<author><name sortKey="Deretic, V" uniqKey="Deretic V">V Deretic</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Vega, Le" uniqKey="Vega L">LE Vega</name>
</author>
<author><name sortKey="Espinoza, Lr" uniqKey="Espinoza L">LR Espinoza</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yen, Yf" uniqKey="Yen Y">YF Yen</name>
</author>
<author><name sortKey="Lan, Yc" uniqKey="Lan Y">YC Lan</name>
</author>
<author><name sortKey="Huang, Ct" uniqKey="Huang C">CT Huang</name>
</author>
<author><name sortKey="Jen, Ia" uniqKey="Jen I">IA Jen</name>
</author>
<author><name sortKey="Chen, M" uniqKey="Chen M">M Chen</name>
</author>
<author><name sortKey="Lee, Cy" uniqKey="Lee C">CY Lee</name>
</author>
<author><name sortKey="Chuang, Ph" uniqKey="Chuang P">PH Chuang</name>
</author>
<author><name sortKey="Lee, Y" uniqKey="Lee Y">Y Lee</name>
</author>
<author><name sortKey="Morisky, De" uniqKey="Morisky D">DE Morisky</name>
</author>
<author><name sortKey="Chen, Ya" uniqKey="Chen Y">YA Chen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yen, Yf" uniqKey="Yen Y">YF Yen</name>
</author>
<author><name sortKey="Chuang, Ph" uniqKey="Chuang P">PH Chuang</name>
</author>
<author><name sortKey="Jen, Ia" uniqKey="Jen I">IA Jen</name>
</author>
<author><name sortKey="Chen, M" uniqKey="Chen M">M Chen</name>
</author>
<author><name sortKey="Lan, Yc" uniqKey="Lan Y">YC Lan</name>
</author>
<author><name sortKey="Liu, Yl" uniqKey="Liu Y">YL Liu</name>
</author>
<author><name sortKey="Lee, Y" uniqKey="Lee Y">Y Lee</name>
</author>
<author><name sortKey="Chen, Yh" uniqKey="Chen Y">YH Chen</name>
</author>
<author><name sortKey="Chen, Ya" uniqKey="Chen Y">YA Chen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chao, A" uniqKey="Chao A">A Chao</name>
</author>
<author><name sortKey="Sieminski, Pj" uniqKey="Sieminski P">PJ Sieminski</name>
</author>
<author><name sortKey="Owens, Cp" uniqKey="Owens C">CP Owens</name>
</author>
<author><name sortKey="Goulding, Cw" uniqKey="Goulding C">CW Goulding</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Skaar, Ep" uniqKey="Skaar E">EP Skaar</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tenhunen, R" uniqKey="Tenhunen R">R Tenhunen</name>
</author>
<author><name sortKey="Marver, Hs" uniqKey="Marver H">HS Marver</name>
</author>
<author><name sortKey="Schmid, R" uniqKey="Schmid R">R Schmid</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Costa, Dl" uniqKey="Costa D">DL Costa</name>
</author>
<author><name sortKey="Namasivayam, S" uniqKey="Namasivayam S">S Namasivayam</name>
</author>
<author><name sortKey="Amaral, Ep" uniqKey="Amaral E">EP Amaral</name>
</author>
<author><name sortKey="Arora, K" uniqKey="Arora K">K Arora</name>
</author>
<author><name sortKey="Chao, A" uniqKey="Chao A">A Chao</name>
</author>
<author><name sortKey="Mittereder, Lr" uniqKey="Mittereder L">LR Mittereder</name>
</author>
<author><name sortKey="Maiga, M" uniqKey="Maiga M">M Maiga</name>
</author>
<author><name sortKey="Boshoff, Hi" uniqKey="Boshoff H">HI Boshoff</name>
</author>
<author><name sortKey="Barry, Ce" uniqKey="Barry C">CE Barry</name>
</author>
<author><name sortKey="Goulding, Cw" uniqKey="Goulding C">CW Goulding</name>
</author>
<author><name sortKey="Andrade, Bb" uniqKey="Andrade B">BB Andrade</name>
</author>
<author><name sortKey="Sher, A" uniqKey="Sher A">A Sher</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Scharn, Cr" uniqKey="Scharn C">CR Scharn</name>
</author>
<author><name sortKey="Collins, Ac" uniqKey="Collins A">AC Collins</name>
</author>
<author><name sortKey="Nair, Vr" uniqKey="Nair V">VR Nair</name>
</author>
<author><name sortKey="Stamm, Ce" uniqKey="Stamm C">CE Stamm</name>
</author>
<author><name sortKey="Marciano, Dk" uniqKey="Marciano D">DK Marciano</name>
</author>
<author><name sortKey="Graviss, Ea" uniqKey="Graviss E">EA Graviss</name>
</author>
<author><name sortKey="Shiloh, Mu" uniqKey="Shiloh M">MU Shiloh</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Regev, D" uniqKey="Regev D">D Regev</name>
</author>
<author><name sortKey="Surolia, R" uniqKey="Surolia R">R Surolia</name>
</author>
<author><name sortKey="Karki, S" uniqKey="Karki S">S Karki</name>
</author>
<author><name sortKey="Zolak, J" uniqKey="Zolak J">J Zolak</name>
</author>
<author><name sortKey="Montes Worboys, A" uniqKey="Montes Worboys A">A Montes-Worboys</name>
</author>
<author><name sortKey="Oliva, O" uniqKey="Oliva O">O Oliva</name>
</author>
<author><name sortKey="Guroji, P" uniqKey="Guroji P">P Guroji</name>
</author>
<author><name sortKey="Saini, V" uniqKey="Saini V">V Saini</name>
</author>
<author><name sortKey="Steyn, Aj" uniqKey="Steyn A">AJ Steyn</name>
</author>
<author><name sortKey="Agarwal, A" uniqKey="Agarwal A">A Agarwal</name>
</author>
<author><name sortKey="Antony, Vb" uniqKey="Antony V">VB Antony</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chinta, Kc" uniqKey="Chinta K">KC Chinta</name>
</author>
<author><name sortKey="Rahman, Ma" uniqKey="Rahman M">MA Rahman</name>
</author>
<author><name sortKey="Saini, V" uniqKey="Saini V">V Saini</name>
</author>
<author><name sortKey="Glasgow, Jn" uniqKey="Glasgow J">JN Glasgow</name>
</author>
<author><name sortKey="Reddy, Vp" uniqKey="Reddy V">VP Reddy</name>
</author>
<author><name sortKey="Lever, Jm" uniqKey="Lever J">JM Lever</name>
</author>
<author><name sortKey="Nhamoyebonde, S" uniqKey="Nhamoyebonde S">S Nhamoyebonde</name>
</author>
<author><name sortKey="Leslie, A" uniqKey="Leslie A">A Leslie</name>
</author>
<author><name sortKey="Wells, Rm" uniqKey="Wells R">RM Wells</name>
</author>
<author><name sortKey="Traylor, A" uniqKey="Traylor A">A Traylor</name>
</author>
<author><name sortKey="Madansein, R" uniqKey="Madansein R">R Madansein</name>
</author>
<author><name sortKey="Siegal, Gp" uniqKey="Siegal G">GP Siegal</name>
</author>
<author><name sortKey="Antony, Vb" uniqKey="Antony V">VB Antony</name>
</author>
<author><name sortKey="Deshane, J" uniqKey="Deshane J">J Deshane</name>
</author>
<author><name sortKey="Wells, G" uniqKey="Wells G">G Wells</name>
</author>
<author><name sortKey="Nargan, K" uniqKey="Nargan K">K Nargan</name>
</author>
<author><name sortKey="George, Jf" uniqKey="George J">JF George</name>
</author>
<author><name sortKey="Ramdial, Pk" uniqKey="Ramdial P">PK Ramdial</name>
</author>
<author><name sortKey="Agarwal, A" uniqKey="Agarwal A">A Agarwal</name>
</author>
<author><name sortKey="Steyn, A" uniqKey="Steyn A">A Steyn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shiloh, Mu" uniqKey="Shiloh M">MU Shiloh</name>
</author>
<author><name sortKey="Manzanillo, P" uniqKey="Manzanillo P">P Manzanillo</name>
</author>
<author><name sortKey="Cox, Js" uniqKey="Cox J">JS Cox</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Waltz, P" uniqKey="Waltz P">P Waltz</name>
</author>
<author><name sortKey="Carchman, Eh" uniqKey="Carchman E">EH Carchman</name>
</author>
<author><name sortKey="Young, Ac" uniqKey="Young A">AC Young</name>
</author>
<author><name sortKey="Rao, J" uniqKey="Rao J">J Rao</name>
</author>
<author><name sortKey="Rosengart, Mr" uniqKey="Rosengart M">MR Rosengart</name>
</author>
<author><name sortKey="Kaczorowski, D" uniqKey="Kaczorowski D">D Kaczorowski</name>
</author>
<author><name sortKey="Zuckerbraun, Bs" uniqKey="Zuckerbraun B">BS Zuckerbraun</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Carchman, Eh" uniqKey="Carchman E">EH Carchman</name>
</author>
<author><name sortKey="Rao, J" uniqKey="Rao J">J Rao</name>
</author>
<author><name sortKey="Loughran, Pa" uniqKey="Loughran P">PA Loughran</name>
</author>
<author><name sortKey="Rosengart, Mr" uniqKey="Rosengart M">MR Rosengart</name>
</author>
<author><name sortKey="Zuckerbraun, Bs" uniqKey="Zuckerbraun B">BS Zuckerbraun</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name>
</author>
<author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name>
</author>
<author><name sortKey="Huang, Zh" uniqKey="Huang Z">ZH Huang</name>
</author>
<author><name sortKey="Huang, Xh" uniqKey="Huang X">XH Huang</name>
</author>
<author><name sortKey="Zheng, Wb" uniqKey="Zheng W">WB Zheng</name>
</author>
<author><name sortKey="Yin, Xf" uniqKey="Yin X">XF Yin</name>
</author>
<author><name sortKey="Li, Yl" uniqKey="Li Y">YL Li</name>
</author>
<author><name sortKey="Li, B" uniqKey="Li B">B Li</name>
</author>
<author><name sortKey="He, Qy" uniqKey="He Q">QY He</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cernigliaro, C" uniqKey="Cernigliaro C">C Cernigliaro</name>
</author>
<author><name sortKey="D Nneo, A" uniqKey="D Nneo A">A D’Anneo</name>
</author>
<author><name sortKey="Carlisi, D" uniqKey="Carlisi D">D Carlisi</name>
</author>
<author><name sortKey="Giuliano, M" uniqKey="Giuliano M">M Giuliano</name>
</author>
<author><name sortKey="Marino Gammazza, A" uniqKey="Marino Gammazza A">A Marino Gammazza</name>
</author>
<author><name sortKey="Barone, R" uniqKey="Barone R">R Barone</name>
</author>
<author><name sortKey="Longhitano, L" uniqKey="Longhitano L">L Longhitano</name>
</author>
<author><name sortKey="Cappello, F" uniqKey="Cappello F">F Cappello</name>
</author>
<author><name sortKey="Emanuele, S" uniqKey="Emanuele S">S Emanuele</name>
</author>
<author><name sortKey="Distefano, A" uniqKey="Distefano A">A Distefano</name>
</author>
<author><name sortKey="Campanella, C" uniqKey="Campanella C">C Campanella</name>
</author>
<author><name sortKey="Calvaruso, G" uniqKey="Calvaruso G">G Calvaruso</name>
</author>
<author><name sortKey="Lauricella, M" uniqKey="Lauricella M">M Lauricella</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dai, Y" uniqKey="Dai Y">Y Dai</name>
</author>
<author><name sortKey="Wen, Z" uniqKey="Wen Z">Z Wen</name>
</author>
<author><name sortKey="Ye, T" uniqKey="Ye T">T Ye</name>
</author>
<author><name sortKey="Deng, G" uniqKey="Deng G">G Deng</name>
</author>
<author><name sortKey="Zhang, M" uniqKey="Zhang M">M Zhang</name>
</author>
<author><name sortKey="Deng, Q" uniqKey="Deng Q">Q Deng</name>
</author>
<author><name sortKey="Yang, Q" uniqKey="Yang Q">Q Yang</name>
</author>
<author><name sortKey="Shan, W" uniqKey="Shan W">W Shan</name>
</author>
<author><name sortKey="Kornfeld, H" uniqKey="Kornfeld H">H Kornfeld</name>
</author>
<author><name sortKey="Cai, Y" uniqKey="Cai Y">Y Cai</name>
</author>
<author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhang, G" uniqKey="Zhang G">G Zhang</name>
</author>
<author><name sortKey="Liu, X" uniqKey="Liu X">X Liu</name>
</author>
<author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name>
</author>
<author><name sortKey="Cai, Y" uniqKey="Cai Y">Y Cai</name>
</author>
<author><name sortKey="Li, S" uniqKey="Li S">S Li</name>
</author>
<author><name sortKey="Chen, Q" uniqKey="Chen Q">Q Chen</name>
</author>
<author><name sortKey="Liao, M" uniqKey="Liao M">M Liao</name>
</author>
<author><name sortKey="Zhang, M" uniqKey="Zhang M">M Zhang</name>
</author>
<author><name sortKey="Zeng, G" uniqKey="Zeng G">G Zeng</name>
</author>
<author><name sortKey="Zhou, B" uniqKey="Zhou B">B Zhou</name>
</author>
<author><name sortKey="Feng, Cg" uniqKey="Feng C">CG Feng</name>
</author>
<author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name>
</author>
<author><name sortKey="Zhang, M" uniqKey="Zhang M">M Zhang</name>
</author>
<author><name sortKey="Liao, M" uniqKey="Liao M">M Liao</name>
</author>
<author><name sortKey="Graner, Mw" uniqKey="Graner M">MW Graner</name>
</author>
<author><name sortKey="Wu, C" uniqKey="Wu C">C Wu</name>
</author>
<author><name sortKey="Yang, Q" uniqKey="Yang Q">Q Yang</name>
</author>
<author><name sortKey="Liu, H" uniqKey="Liu H">H Liu</name>
</author>
<author><name sortKey="Zhou, B" uniqKey="Zhou B">B Zhou</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Youssef, La" uniqKey="Youssef L">LA Youssef</name>
</author>
<author><name sortKey="Rebbaa, A" uniqKey="Rebbaa A">A Rebbaa</name>
</author>
<author><name sortKey="Pampou, S" uniqKey="Pampou S">S Pampou</name>
</author>
<author><name sortKey="Weisberg, Sp" uniqKey="Weisberg S">SP Weisberg</name>
</author>
<author><name sortKey="Stockwell, Br" uniqKey="Stockwell B">BR Stockwell</name>
</author>
<author><name sortKey="Hod, Ea" uniqKey="Hod E">EA Hod</name>
</author>
<author><name sortKey="Spitalnik, Sl" uniqKey="Spitalnik S">SL Spitalnik</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roback, Jd" uniqKey="Roback J">JD Roback</name>
</author>
<author><name sortKey="Barclay, S" uniqKey="Barclay S">S Barclay</name>
</author>
<author><name sortKey="Moulds, Jm" uniqKey="Moulds J">JM Moulds</name>
</author>
<author><name sortKey="Denomme, Ga" uniqKey="Denomme G">GA Denomme</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mishra, Bb" uniqKey="Mishra B">BB Mishra</name>
</author>
<author><name sortKey="Lovewell, Rr" uniqKey="Lovewell R">RR Lovewell</name>
</author>
<author><name sortKey="Olive, Aj" uniqKey="Olive A">AJ Olive</name>
</author>
<author><name sortKey="Zhang, G" uniqKey="Zhang G">G Zhang</name>
</author>
<author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name>
</author>
<author><name sortKey="Eugenin, E" uniqKey="Eugenin E">E Eugenin</name>
</author>
<author><name sortKey="Smith, Cm" uniqKey="Smith C">CM Smith</name>
</author>
<author><name sortKey="Phuah, Jy" uniqKey="Phuah J">JY Phuah</name>
</author>
<author><name sortKey="Long, Je" uniqKey="Long J">JE Long</name>
</author>
<author><name sortKey="Dubuke, Ml" uniqKey="Dubuke M">ML Dubuke</name>
</author>
<author><name sortKey="Palace, Sg" uniqKey="Palace S">SG Palace</name>
</author>
<author><name sortKey="Goguen, Jd" uniqKey="Goguen J">JD Goguen</name>
</author>
<author><name sortKey="Baker, Re" uniqKey="Baker R">RE Baker</name>
</author>
<author><name sortKey="Nambi, S" uniqKey="Nambi S">S Nambi</name>
</author>
<author><name sortKey="Mishra, R" uniqKey="Mishra R">R Mishra</name>
</author>
<author><name sortKey="Booty, Mg" uniqKey="Booty M">MG Booty</name>
</author>
<author><name sortKey="Baer, Ce" uniqKey="Baer C">CE Baer</name>
</author>
<author><name sortKey="Shaffer, Sa" uniqKey="Shaffer S">SA Shaffer</name>
</author>
<author><name sortKey="Dartois, V" uniqKey="Dartois V">V Dartois</name>
</author>
<author><name sortKey="Mccormick, Ba" uniqKey="Mccormick B">BA McCormick</name>
</author>
<author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name>
</author>
<author><name sortKey="Sassetti, Cm" uniqKey="Sassetti C">CM Sassetti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cai, Y" uniqKey="Cai Y">Y Cai</name>
</author>
<author><name sortKey="Yang, Q" uniqKey="Yang Q">Q Yang</name>
</author>
<author><name sortKey="Liao, M" uniqKey="Liao M">M Liao</name>
</author>
<author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name>
</author>
<author><name sortKey="Zhang, C" uniqKey="Zhang C">C Zhang</name>
</author>
<author><name sortKey="Nambi, S" uniqKey="Nambi S">S Nambi</name>
</author>
<author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name>
</author>
<author><name sortKey="Zhang, M" uniqKey="Zhang M">M Zhang</name>
</author>
<author><name sortKey="Wu, J" uniqKey="Wu J">J Wu</name>
</author>
<author><name sortKey="Deng, G" uniqKey="Deng G">G Deng</name>
</author>
<author><name sortKey="Deng, Q" uniqKey="Deng Q">Q Deng</name>
</author>
<author><name sortKey="Liu, H" uniqKey="Liu H">H Liu</name>
</author>
<author><name sortKey="Zhou, B" uniqKey="Zhou B">B Zhou</name>
</author>
<author><name sortKey="Jin, Q" uniqKey="Jin Q">Q Jin</name>
</author>
<author><name sortKey="Feng, Cg" uniqKey="Feng C">CG Feng</name>
</author>
<author><name sortKey="Sassetti, Cm" uniqKey="Sassetti C">CM Sassetti</name>
</author>
<author><name sortKey="Wang, F" uniqKey="Wang F">F Wang</name>
</author>
<author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name>
</author>
<author><name sortKey="Dong, Q" uniqKey="Dong Q">Q Dong</name>
</author>
<author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name>
</author>
<author><name sortKey="He, Y" uniqKey="He Y">Y He</name>
</author>
<author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name>
</author>
<author><name sortKey="Zhang, H" uniqKey="Zhang H">H Zhang</name>
</author>
<author><name sortKey="Wu, R" uniqKey="Wu R">R Wu</name>
</author>
<author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name>
</author>
<author><name sortKey="Zhou, B" uniqKey="Zhou B">B Zhou</name>
</author>
<author><name sortKey="He, J" uniqKey="He J">J He</name>
</author>
<author><name sortKey="Kung, Hf" uniqKey="Kung H">HF Kung</name>
</author>
<author><name sortKey="Huang, C" uniqKey="Huang C">C Huang</name>
</author>
<author><name sortKey="Wei, Y" uniqKey="Wei Y">Y Wei</name>
</author>
<author><name sortKey="Huang, Jd" uniqKey="Huang J">JD Huang</name>
</author>
<author><name sortKey="Xu, H" uniqKey="Xu H">H Xu</name>
</author>
<author><name sortKey="He, Ml" uniqKey="He M">ML He</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhang, G" uniqKey="Zhang G">G Zhang</name>
</author>
<author><name sortKey="Zhou, B" uniqKey="Zhou B">B Zhou</name>
</author>
<author><name sortKey="Li, S" uniqKey="Li S">S Li</name>
</author>
<author><name sortKey="Yue, J" uniqKey="Yue J">J Yue</name>
</author>
<author><name sortKey="Yang, H" uniqKey="Yang H">H Yang</name>
</author>
<author><name sortKey="Wen, Y" uniqKey="Wen Y">Y Wen</name>
</author>
<author><name sortKey="Zhan, S" uniqKey="Zhan S">S Zhan</name>
</author>
<author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name>
</author>
<author><name sortKey="Liao, M" uniqKey="Liao M">M Liao</name>
</author>
<author><name sortKey="Zhang, M" uniqKey="Zhang M">M Zhang</name>
</author>
<author><name sortKey="Zeng, G" uniqKey="Zeng G">G Zeng</name>
</author>
<author><name sortKey="Feng, Cg" uniqKey="Feng C">CG Feng</name>
</author>
<author><name sortKey="Sassetti, Cm" uniqKey="Sassetti C">CM Sassetti</name>
</author>
<author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
  <front><journal-meta><journal-id journal-id-type="nlm-ta">mBio</journal-id>
<journal-id journal-id-type="iso-abbrev">mBio</journal-id>
<journal-id journal-id-type="hwp">mbio</journal-id>
<journal-id journal-id-type="pmc">mbio</journal-id>
<journal-id journal-id-type="publisher-id">mBio</journal-id>
<journal-title-group><journal-title>mBio</journal-title>
</journal-title-group>
<issn pub-type="epub">2150-7511</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">32098821</article-id>
<article-id pub-id-type="pmc">7042700</article-id>
<article-id pub-id-type="publisher-id">mBio03246-19</article-id>
<article-id pub-id-type="doi">10.1128/mBio.03246-19</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="overline"><subject>Host-Microbe Biology</subject>
</subj-group>
</article-categories>
<title-group><article-title>Autoantibody-Mediated Erythrophagocytosis Increases Tuberculosis Susceptibility in HIV Patients</article-title>
<alt-title alt-title-type="running-head">HIV Impairs TB Immunity via Erythrophagocytosis</alt-title>
<alt-title alt-title-type="short-authors">Dai et al.</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Dai</surname>
<given-names>Youchao</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Cai</surname>
<given-names>Yi</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Wang</surname>
<given-names>Xin</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Zhu</surname>
<given-names>Jialou</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Liu</surname>
<given-names>Xiaoqing</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Liu</surname>
<given-names>Houming</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>f</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Li</surname>
<given-names>Linghua</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Zhang</surname>
<given-names>Yinze</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Liu</surname>
<given-names>Shengze</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>g</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Wen</surname>
<given-names>Zhihua</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>g</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="no"><name><surname>Feng</surname>
<given-names>Carl G.</given-names>
</name>
<xref ref-type="aff" rid="aff8"><sup>h</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes" equal-contrib="no"><name><surname>Chen</surname>
<given-names>Xinchun</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes" equal-contrib="no"><name><surname>Tang</surname>
<given-names>Xiaoping</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<aff id="aff1"><label>a</label>
<addr-line>Research Institute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, China</addr-line>
</aff>
<aff id="aff2"><label>b</label>
<addr-line>Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China</addr-line>
</aff>
<aff id="aff3"><label>c</label>
<addr-line>International Cancer Center, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China</addr-line>
</aff>
<aff id="aff4"><label>d</label>
<addr-line>Department of Infectious Disease, Shenzhen People’s Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China</addr-line>
</aff>
<aff id="aff5"><label>e</label>
<addr-line>Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, Guangdong Province, China</addr-line>
</aff>
<aff id="aff6"><label>f</label>
<addr-line>Clinical Laboratory, Shenzhen Third People’s Hospital, Shenzhen University School of Medicine, Shenzhen, China</addr-line>
</aff>
<aff id="aff7"><label>g</label>
<addr-line>Yuebei Second People’s Hospital, Shaoguan, China</addr-line>
</aff>
<aff id="aff8"><label>h</label>
<addr-line>Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia</addr-line>
</aff>
</contrib-group>
<contrib-group><contrib contrib-type="editor"><name><surname>Kaufmann</surname>
<given-names>Stefan H. E.</given-names>
</name>
<role>Editor</role>
<aff>Max Planck Institute for Infection Biology</aff>
</contrib>
</contrib-group>
<author-notes><corresp id="cor1">Address correspondence to Xinchun Chen, <email>chenxinchun@szu.edu.cn</email>
, or Xiaoping Tang, <email>tangxiaopinggz@163.com</email>
.</corresp>
<fn fn-type="equal"><p>Youchao Dai and Yi Cai contributed equally to this article. Author order was determined by the temporal order in which the authors began performing the research.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><season>Jan-Feb</season>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub"><day>25</day>
<month>2</month>
<year>2020</year>
</pub-date>
<volume>11</volume>
<issue>1</issue>
<elocation-id>e03246-19</elocation-id>
<history><date date-type="received"><day>10</day>
<month>12</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>15</day>
<month>1</month>
<year>2020</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2020 Dai et al.</copyright-statement>
<copyright-year>2020</copyright-year>
<copyright-holder>Dai et al.</copyright-holder>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link>
.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="mBio.03246-19.pdf"></self-uri>
<abstract abstract-type="precis"><p>HIV infection significantly increases TB susceptibility due to CD4 T-cell loss and macrophage dysfunction. Although it is relatively clear that CD4 T-cell loss represents a direct effect of HIV infection, the mechanism underlying how HIV infection dampens macrophage function is unknown. Here, we show that HIV infection enhances autoantibody-mediated erythrophagocytosis, which dampens macrophage bactericidal activity against TB by inhibiting HO-1-associated autophagy. Our findings reveal a novel mechanism explaining how HIV infection increases susceptibility to TB. We propose that DAT could be a potential measure to identify HIV patients who are at high TB risk and who would be suitable for anti-TB chemotherapy preventive treatment.</p>
</abstract>
<abstract><title>ABSTRACT</title>
<p>Macrophage dysfunction is associated with increased tuberculosis (TB) susceptibility in patients with human immunodeficiency virus (HIV) infection. However, the mechanisms underlying how HIV infection impairs macrophage function are unclear. Here, we found that levels of autoantibodies against red blood cells (RBCs) were significantly elevated in patients with HIV as determined by direct antiglobulin test (DAT). DAT positivity was significantly associated with TB incidence in both univariate and multivariate analyses (odds ratio [OR] = 11.96 [confidence interval {CI}, 4.68 to 30.93] and 12.65 [3.33 to 52.75], respectively). <italic>Ex vivo</italic>
 analysis showed that autoantibodies against RBCs enhanced erythrophagocytosis and thus significantly impaired macrophage bactericidal function against intracellular <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>
. Mechanistically, autoantibody-mediated erythrophagocytosis increased heme oxygenase-1 (HO-1) expression, which inhibited <named-content content-type="genus-species">M. tuberculosis</named-content>
-induced autophagy in macrophages. Silencing <italic>ATG5</italic>
, a key component for autophagy, completely abrogated the effect of erythrophagocytosis on macrophage bactericidal activity against <named-content content-type="genus-species">M. tuberculosis</named-content>
. In conclusion, we have demonstrated that HIV infection increases autoantibody-mediated erythrophagocytosis. This process impairs macrophage bactericidal activity against <named-content content-type="genus-species">M. tuberculosis</named-content>
 by inhibiting HO-1-associated autophagy. These findings reveal a novel mechanism as to how HIV infection increases TB susceptibility.</p>
</abstract>
<kwd-group><title>KEYWORDS</title>
<kwd>HIV</kwd>
<kwd>erythrophagocytosis</kwd>
<kwd>heme oxygenase-1</kwd>
<kwd>autophagy</kwd>
<kwd>tuberculosis</kwd>
</kwd-group>
<funding-group><award-group id="award1"><funding-source><institution-wrap><institution>Science and Technology Project of Shenzhen</institution>
</institution-wrap>
</funding-source>
<award-id>JCYJ20160427184123851</award-id>
<principal-award-recipient><name><surname>Cai</surname>
<given-names>Yi</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award2"><funding-source><institution-wrap><institution>Science and Technology Project of Shenzhen</institution>
</institution-wrap>
</funding-source>
<award-id>JCYJ20160427151540695</award-id>
<principal-award-recipient><name><surname>Liu</surname>
<given-names>Houming</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award3"><funding-source><institution-wrap><institution>Science and Technology Project of Shenzhen</institution>
</institution-wrap>
</funding-source>
<award-id>JCYJ20170307095303424</award-id>
<principal-award-recipient><name><surname>Chen</surname>
<given-names>Xinchun</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award4"><funding-source><institution-wrap><institution>Natural Science Foundation of China</institution>
</institution-wrap>
</funding-source>
<award-id>81525016/81772145/91942315</award-id>
<principal-award-recipient><name><surname>Chen</surname>
<given-names>Xinchun</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award5"><funding-source><institution-wrap><institution>Natural Science Foundation of China</institution>
</institution-wrap>
</funding-source>
<award-id>81770013</award-id>
<principal-award-recipient><name><surname>Cai</surname>
<given-names>Yi</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award6"><funding-source><institution-wrap><institution>Natural Science Foundation of China</institution>
</institution-wrap>
</funding-source>
<award-id>81871255</award-id>
<principal-award-recipient><name><surname>Feng</surname>
<given-names>Carl</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<counts><count count="8" count-type="supplementary-material"></count>
<fig-count count="5"></fig-count>
<table-count count="1"></table-count>
<equation-count count="0"></equation-count>
<ref-count count="61"></ref-count>
<page-count count="14"></page-count>
<word-count count="10576"></word-count>
</counts>
<custom-meta-group><custom-meta><meta-name>cover-date</meta-name>
<meta-value>January/February 2020</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body><sec sec-type="intro" id="s1"><title>INTRODUCTION</title>
<p>Tuberculosis (TB) caused by <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>
 infection is one of the 10 most common causes of mortality worldwide and the leading cause of mortality from a single infectious agent; ∼10 million new cases were reported in 2017, with 1.6 million deaths (<xref rid="B1" ref-type="bibr">1</xref>
). Human immunodeficiency virus (HIV) infection is a strong risk factor for disease progression in TB and is thus associated with poor treatment outcomes (<xref rid="B2" ref-type="bibr">2</xref>
<xref ref-type="bibr" rid="B3">–</xref>
<xref rid="B4" ref-type="bibr">4</xref>
). The HIV-mediated depletion of CD4 T cells that typically confers a protective immune response to <named-content content-type="genus-species">M. tuberculosis</named-content>
 infection is likely a main driver of the increased prevalence of active TB in countries with a high HIV burden (<xref rid="B5" ref-type="bibr">5</xref>
<xref ref-type="bibr" rid="B6">–</xref>
<xref rid="B7" ref-type="bibr">7</xref>
). Interestingly, increased TB risk has also been reported among patients with HIV and normal CD4 T-cell counts (<xref rid="B8" ref-type="bibr">8</xref>
, <xref rid="B9" ref-type="bibr">9</xref>
). Indeed, besides CD4 T-cell loss, macrophage function is altered during HIV infection also (<xref rid="B10" ref-type="bibr">10</xref>
, <xref rid="B11" ref-type="bibr">11</xref>
). Macrophage-driven innate immunity has been increasingly recognized as having a critical role in the host defense against TB (<xref rid="B12" ref-type="bibr">12</xref>
); fine-tuning of macrophage fate and function is essential to <named-content content-type="genus-species">M. tuberculosis</named-content>
 infection outcomes (<xref rid="B13" ref-type="bibr">13</xref>
). However, the mechanisms underlying how HIV infection impairs macrophage-mediated defenses against <named-content content-type="genus-species">M. tuberculosis</named-content>
 remain to be elucidated.</p>
<p>HIV infection can induce the production of various autoantibodies, which leads to the development of autoimmune diseases (<xref rid="B14" ref-type="bibr">14</xref>
). It is reported that 20% to 40% of patients with HIV are positive for anti-red blood cell (RBC) autoantibodies, which can be detected using a direct antiglobulin test (DAT) (<xref rid="B15" ref-type="bibr">15</xref>
, <xref rid="B16" ref-type="bibr">16</xref>
). Treatment with heme, a major component of lysed RBCs, triggers macrophage death, with characteristics of programmed necrosis, and inhibits bactericidal activity against <named-content content-type="genus-species">M. tuberculosis</named-content>
 (<xref rid="B17" ref-type="bibr">17</xref>
). In addition, stored RBCs for transfusion can suppress the macrophage defense against <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
 infection though elevated circulating heme levels (<xref rid="B18" ref-type="bibr">18</xref>
). The presence of anti-RBC autoantibodies can sensitize RBCs <italic>in vivo</italic>
 and trigger accelerated RBC phagocytosis and destruction by macrophages (<xref rid="B19" ref-type="bibr">19</xref>
, <xref rid="B20" ref-type="bibr">20</xref>
). We therefore hypothesized that anti-RBC autoantibodies might impair macrophage functions to fight against TB by enhancing erythrophagocytosis (macrophagic engulfment of RBCs).</p>
<p>To test our hypothesis, first, we investigated the association between the presence of anti-RBC autoantibodies and the increased risk of TB in patients with HIV. Second, we determined the effect and mechanism of erythrophagocytosis enhanced by anti-RBC autoantibodies on macrophage bactericidal activity against <named-content content-type="genus-species">M. tuberculosis</named-content>
.</p>
</sec>
<sec sec-type="results" id="s2"><title>RESULTS</title>
<sec id="s2.1"><title>Enhanced anti-RBC autoantibody production in patients with HIV is associated with increased risk of development of active TB.</title>
<p>We first aimed to investigate the presence of anti-RBC autoantibodies in patients with HIV and its association with TB susceptibility. DATs were used to detect anti-RBC autoantibodies in 267 HIV-seropositive patients with (<italic>n</italic>
 = 23, 9%) or without (<italic>n</italic>
 = 244, 91%) TB. Here, 28/267 cases (10%) were DAT positive, but DAT positivity was significantly higher in HIV patients with TB than in those without TB (48% versus 7%, <italic>P</italic>
 < 0.001) (<xref rid="tab1" ref-type="table">Table 1</xref>
).</p>
<table-wrap id="tab1" orientation="portrait" position="float"><label>TABLE 1</label>
<caption><p>Univariate and multivariate logistic regression analysis of factors associated with TB susceptibility in HIV patients<xref ref-type="table-fn" rid="ngtab1.1"><sup><italic>a</italic>
</sup>
</xref>
</p>
</caption>
<alternatives><table frame="hsides" rules="groups"><colgroup span="1"><col span="1"></col>
<col span="1"></col>
<col span="1"></col>
<col span="1"></col>
<col span="1"></col>
<col span="1"></col>
<col span="1"></col>
</colgroup>
<thead><tr><th rowspan="2" colspan="1">Parameter</th>
<th colspan="6" rowspan="1">Value(s)<hr></hr>
</th>
</tr>
<tr><th rowspan="1" colspan="1">HIV<break></break>
without TB<break></break>
(<italic>n</italic>
 = 244)</th>
<th rowspan="1" colspan="1">HIV<break></break>
with TB<xref ref-type="table-fn" rid="ngtab1.2"><sup><italic>b</italic>
</sup>
</xref>
<break></break>
(<italic>n</italic>
 = 23)</th>
<th rowspan="1" colspan="1">Univariate<break></break>
analysis<break></break>
OR [95% CI]</th>
<th rowspan="1" colspan="1"><italic>P</italic>
</th>
<th rowspan="1" colspan="1">Multivariate<break></break>
analysis<break></break>
[95% CI]<xref ref-type="table-fn" rid="ngtab1.3"><sup><italic>c</italic>
</sup>
</xref>
</th>
<th rowspan="1" colspan="1"><italic>P</italic>
</th>
</tr>
</thead>
<tbody><tr><td rowspan="1" colspan="1">No. of males/total no. of patients (%)</td>
<td rowspan="1" colspan="1">185/244 (76)</td>
<td rowspan="1" colspan="1">19/23 (83)</td>
<td rowspan="1" colspan="1">1.39 [0.52–4.59]</td>
<td rowspan="1" colspan="1">0.533</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td rowspan="1" colspan="1">Yrs of age (range)</td>
<td rowspan="1" colspan="1">40 (32–48)</td>
<td rowspan="1" colspan="1">34 (29–42)</td>
<td rowspan="1" colspan="1">0.95 [0.90–0.99]</td>
<td rowspan="1" colspan="1"><bold>0.008</bold>
</td>
<td rowspan="1" colspan="1">0.95 [0.90–1.00]</td>
<td rowspan="1" colspan="1"><bold>0.038</bold>
</td>
</tr>
<tr><td rowspan="1" colspan="1">Log HIV load (range)</td>
<td rowspan="1" colspan="1">4.69 (3.96–5.28)</td>
<td rowspan="1" colspan="1">4.18 (3.97–4.98)</td>
<td rowspan="1" colspan="1">1.07 [0.82–1.49]</td>
<td rowspan="1" colspan="1">0.668</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td rowspan="1" colspan="1">WBC count at 10<sup>9</sup>
/liter (range)</td>
<td rowspan="1" colspan="1">7.90 (6.07–9.20)</td>
<td rowspan="1" colspan="1">9.20 (6.70–10.75)</td>
<td rowspan="1" colspan="1">1.21 [1.02–1.43]</td>
<td rowspan="1" colspan="1"><bold>0.030</bold>
</td>
<td rowspan="1" colspan="1">1.16 [0.96–1.40]</td>
<td rowspan="1" colspan="1">0.121</td>
</tr>
<tr><td rowspan="1" colspan="1">Hemoglobin levels in g/liter (range)</td>
<td rowspan="1" colspan="1">139 (129–152)</td>
<td rowspan="1" colspan="1">138 (115–147)</td>
<td rowspan="1" colspan="1">0.98 [0.96–1.00]</td>
<td rowspan="1" colspan="1"><bold>0.041</bold>
</td>
<td rowspan="1" colspan="1">1.03 [0.99–1.08]</td>
<td rowspan="1" colspan="1">0.121</td>
</tr>
<tr><td rowspan="1" colspan="1">No. of patients with anemia/total no. of patients (%)<xref ref-type="table-fn" rid="ngtab1.4"><sup><italic>d</italic>
</sup>
</xref>
</td>
<td rowspan="1" colspan="1">35/244 (14)</td>
<td rowspan="1" colspan="1">10/23 (44)</td>
<td rowspan="1" colspan="1">4.59 [1.87–11.08]</td>
<td rowspan="1" colspan="1"><bold>0.001</bold>
</td>
<td rowspan="1" colspan="1">3.32 [0.54–21.21]</td>
<td rowspan="1" colspan="1">0.193</td>
</tr>
<tr><td rowspan="1" colspan="1">No. of CD4 T cells/μl (range)<xref ref-type="table-fn" rid="ngtab1.5"><sup><italic>e</italic>
</sup>
</xref>
</td>
<td rowspan="1" colspan="1">357 (198–698)</td>
<td rowspan="1" colspan="1">436 (259–835)</td>
<td rowspan="1" colspan="1">1.00 [1.00–1.00]</td>
<td rowspan="1" colspan="1">0.325</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td rowspan="1" colspan="1">No. (%) of DAT-positive results</td>
<td rowspan="1" colspan="1">17/244 (7)</td>
<td rowspan="1" colspan="1">11/23 (48)</td>
<td rowspan="1" colspan="1">11.96 [4.68–30.93]</td>
<td rowspan="1" colspan="1"><bold><0.001</bold>
</td>
<td rowspan="1" colspan="1">12.65 [3.33–52.75]</td>
<td rowspan="1" colspan="1"><bold><0.001</bold>
</td>
</tr>
</tbody>
</table>
<graphic xlink:href="mBio.03246-19-t0001"></graphic>
</alternatives>
<table-wrap-foot><fn fn-type="other" id="ngtab1.1"><label>a</label>
<p>TB, tuberculosis; HIV, human immunodeficiency virus; OR, odds ratio; CI, confidence interval; WBC, white blood cell; RBC, red blood cell; DAT, direct antiglobulin test. Categorical variables are expressed as absolute numbers and percentages, whereas continuous variables are reported as medians and interquartile ranges. Significant differences (<italic>P</italic>
 < 0.1 in univariable analysis and <italic>P</italic>
 < 0.05 in multivariable analysis) are highlighted in bold.</p>
</fn>
<fn fn-type="other" id="ngtab1.2"><label>b</label>
<p>TB was diagnosed by experienced specialists if (i) sputum samples were positive for AFB, NAAT, or <named-content content-type="genus-species">M. tuberculosis</named-content>
 culture (ii) or results showed no sputum or negative smear results but showed high-resolution computed tomography (HRCT) evidence, positive IGRA, and symptoms responding to TB treatment.</p>
</fn>
<fn fn-type="other" id="ngtab1.3"><label>c</label>
<p>The likelihood ratio test had a <italic>P</italic>
 value of <0.0001, and The Hosmer and Lemeshow goodness-of-fit (GOF) test had a <italic>P</italic>
 value = 0.7206. Both tests indicated that the multivariable logistic regression model was a good fit to the data.</p>
</fn>
<fn fn-type="other" id="ngtab1.4"><label>d</label>
<p>Anemia was diagnosed at hemoglobin levels of <130 g/liter for males and <115 g/liter for females.</p>
</fn>
<fn fn-type="other" id="ngtab1.5"><label>e</label>
<p>CD4 T-cell data were missing for 19 cases in HIV without TB and three cases in HIV with TB.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>To determine the risk of TB in patients with HIV, various clinical parameters with potential to affect the host defense system were obtained and input into a univariate model to calculate the risk odds ratio (OR) (<xref rid="tab1" ref-type="table">Table 1</xref>
). In line with a previous report (<xref rid="B21" ref-type="bibr">21</xref>
), anemia was significantly associated with TB (OR = 4.59 [confidence interval {CI}, 1.87 to 11.08], <italic>P</italic>
 < 0.001); however, following adjustment for other variables in the multivariate analysis, anemia was not significantly associated with TB incidence (OR = 3.32 [0.54 to 21.21], <italic>P</italic>
 = 0.121). By comparison, DAT positivity was significantly associated with TB incidence in both univariate and multivariate analyses (OR = 11.96 [4.68 to 30.93] and 12.65 [3.33 to 52.75], respectively; both <italic>P</italic>
 < 0.001). Therefore, extending previous findings on the association between anemia and DAT (<xref rid="B16" ref-type="bibr">16</xref>
, <xref rid="B22" ref-type="bibr">22</xref>
), our data provide evidence that increased anti-RBC autoantibody production in HIV is associated with increased TB risk.</p>
</sec>
<sec id="s2.2"><title>Enhanced erythrophagocytosis in patients with HIV is mediated by anti-RBC autoantibodies.</title>
<p>To dissect the causal relationship between anti-RBC autoantibodies and TB susceptibility, we examined macrophage function. Macrophages have critical roles in fighting against <named-content content-type="genus-species">M. tuberculosis</named-content>
 and clearing senescent or damaged RBCs (<xref rid="B12" ref-type="bibr">12</xref>
, <xref rid="B23" ref-type="bibr">23</xref>
). A positive DAT result indicates RBC sensitization by autoantibodies that trigger accelerated RBC phagocytosis and destruction by macrophages (<xref rid="B19" ref-type="bibr">19</xref>
, <xref rid="B20" ref-type="bibr">20</xref>
). We labeled RBCs isolated from 33 healthy donors and 47 HIV-seropositive patients (including 36 DAT-negative and 11 DAT-positive cases) with a membrane-integrating dye (PKH-26) (<xref ref-type="fig" rid="fig1">Fig. 1A</xref>
) and determined RBC uptake by phorbol myristate acetate (PMA)-differentiated THP-1 macrophages by flow cytometry (see <xref ref-type="supplementary-material" rid="tabS1">Table S1</xref>
 in the supplemental material).</p>
<fig id="fig1" orientation="portrait" position="float"><label>FIG 1</label>
<caption><p>RBCs from patients with HIV with a positive direct antiglobulin test (DAT) result increase erythrophagocytosis by macrophages. (A) RBCs labeled with a membrane-integrating dye (PKH-26) were assessed by confocal fluorescence microscopy (left; bars, 2 μm) and flow cytometry (right; labeling yield, 99.6%). (B and C) <italic>Ex vivo</italic>
 phagocytosis of PKH-26-labeled RBCs from healthy donors (<italic>n</italic>
 = 33) and patients with HIV with negative (<italic>n</italic>
 = 36) and positive (<italic>n</italic>
 = 11) DAT results upon incubation with PMA-differentiated THP-1 macrophages for 6 h at RBC/macrophage (R/M) ratios of 10:1 and 100:1 revealed by forward scatter (FSC) data (B) and quantified by flow cytometry (C). (D) DAT results were classified as negative (−) or positive (with 1+ [+], 2+ [++], and 3+ [+++] degrees) corresponding to the RBC agglutination strength. (E) Correlation between erythrophagocytosis rate and DAT agglutination level at both R/M ratios (orange, R/M ratio = 10:1; purple, R/M ratio = 100:1), assessed using Spearman’s rank correlation. The data represent means ± standard deviations and are representative of results from at least three independent experiments. ***<italic>*</italic>
, <italic>P < </italic>
0.0001.</p>
</caption>
<graphic xlink:href="mBio.03246-19-f0001"></graphic>
</fig>
<supplementary-material content-type="local-data" id="tabS1"><object-id pub-id-type="doi">10.1128/mBio.03246-19.8</object-id>
<label>TABLE S1</label>
<p>Demographics and clinical characteristics of the subjects selected for erythrophagocytosis assay. Download <inline-supplementary-material id="tS1" mimetype="application" mime-subtype="vnd.ms-word" xlink:href="mBio.03246-19-st001.doc" content-type="local-data">Table S1, DOC file, 0.04 MB</inline-supplementary-material>
.</p>
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<copyright-holder>Dai et al.</copyright-holder>
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.</license-p>
</license>
</permissions>
</supplementary-material>
<p>We found that the percentage of phagocytosis of RBCs from DAT-positive patients with HIV was significantly higher than the percentage seen with RBCs from healthy donors and DAT-negative patients with HIV (<xref ref-type="fig" rid="fig1">Fig. 1B</xref>
 and <xref ref-type="fig" rid="fig1">C</xref>
). No significant differences in erythrophagocytosis were observed between DAT-negative patients with HIV and healthy donors (<xref ref-type="fig" rid="fig1">Fig. 1B</xref>
 and <xref ref-type="fig" rid="fig1">C</xref>
). TB status did not influence the differences in erythrophagocytosis between HIV patients with TB and those without TB, which might have been due to the limited number of cases (<italic>n</italic>
 = 5) of HIV-TB (see <xref ref-type="supplementary-material" rid="figS1">Fig. S1</xref>
 in the supplemental material). The DAT reactions were classified in ascending degrees from negative (-) to positive, with 1+, 2+, and 3+ corresponding to the levels of agglutination strength of RBCs (<xref ref-type="fig" rid="fig1">Fig. 1D</xref>
). We found that the extent of erythrophagocytosis was significantly correlated with the agglutination degree of DAT (<italic>R</italic>
 = 0.99 and <italic>P</italic>
 < 0.01 for both) (<xref ref-type="fig" rid="fig1">Fig. 1E</xref>
), indicating the importance of autoantibodies in erythrophagocytosis.</p>
<supplementary-material content-type="local-data" id="figS1"><object-id pub-id-type="doi">10.1128/mBio.03246-19.1</object-id>
<label>FIG S1</label>
<p>TB status has no effect on macrophage-mediated phagocytosis of RBCs from patients with HIV. Data represent <italic>ex vivo</italic>
 phagocytosis of PKH-26-labeled RBCs from healthy donors (<italic>n</italic>
 = 33) and HIV patients with TB (<italic>n</italic>
 = 5) or without TB (<italic>n</italic>
 = 42) upon incubation with PMA-differentiated THP-1 macrophages for 6 h at RBC/macrophage (R/M) ratios of 10:1 and 100:1, respectively. Download <inline-supplementary-material id="fS1" mimetype="image" mime-subtype="tif" xlink:href="mBio.03246-19-sf001.tif" content-type="local-data">FIG S1, TIF file, 1.1 MB</inline-supplementary-material>
.</p>
<permissions><copyright-statement>Copyright © 2020 Dai et al.</copyright-statement>
<copyright-year>2020</copyright-year>
<copyright-holder>Dai et al.</copyright-holder>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><license-p>This content is distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link>
.</license-p>
</license>
</permissions>
</supplementary-material>
<p>We further demonstrated a role for anti-RBC autoantibodies in erythrophagocytosis <italic>in vitro</italic>
 by preincubating RBCs from healthy donors with commercial anti-human RBC IgG to mimic RBC sensitization <italic>in vivo</italic>
. These sensitized RBCs (sRBCs) were more susceptible to erythrophagocytosis than nonsensitized RBCs incubated with vehicle (phosphate-buffered saline [PBS]) or isotype rabbit IgG (<xref ref-type="fig" rid="fig2">Fig. 2A</xref>
 and <xref ref-type="fig" rid="fig2">B</xref>
). This increase in erythrophagocytosis was both anti-RBC IgG dose dependent and time dependent (<xref ref-type="fig" rid="fig2">Fig. 2B</xref>
 and <xref ref-type="fig" rid="fig2">C</xref>
). We then used Fcγ receptor blocking antibodies to block the Fcγ receptors on macrophages that sense antibody-RBC immunocomplexes and mediate RBC phagocytosis. Here, we found that the erythrophagocytosis of RBCs purified from DAT-positive patients with HIV and sRBCs by anti-RBC IgG was completely inhibited, whereas erythrophagocytosis of RBCs from healthy donors was not affected by Fcγ receptor blocker treatment (<xref ref-type="fig" rid="fig2">Fig. 2D</xref>
 and <xref ref-type="fig" rid="fig2">E</xref>
). In contrast, the complement receptor was not involved in erythrophagocytosis (<xref ref-type="supplementary-material" rid="figS2">Fig. S2</xref>
). Taken together, these results demonstrate that enhanced erythrophagocytosis in DAT-positive patients with HIV is mediated by anti-RBC autoantibodies. In addition, the data suggest that sRBCs constitute a reliable model to further study erythrophagocytosis.</p>
<fig id="fig2" orientation="portrait" position="float"><label>FIG 2</label>
<caption><p>Enhanced erythrophagocytosis in patients with HIV can be blocked by neutralizing Fcγ receptors on macrophages. (A and B) RBCs from healthy donors were sensitized with different concentrations of anti-human RBC IgG (0, 25, 375, and 1,500 μg/ml) or isotype rabbit IgG (375 μg/ml) and were then labeled with PKH-26. <italic>In vitro</italic>
 phagocytosis of the indicated RBCs after incubation with PMA-differentiated THP-1 macrophages for 6 h at an RBC/macrophage (R/M) ratio of 100:1 was revealed by forward scatter data (A) and quantified by flow cytometry (B). (C) Erythrophagocytosis analysis was performed at various time points (0.5, 1, 2, 6, 12, and 24 h) after treatment of sensitized RBCs (sRBCs) (anti-human RBC IgG, 1,500 μg/ml) at an R/M ratio of 100:1, as assessed by flow cytometry. (D and E) PMA-differentiated THP-1 macrophages were treated with the indicated dilution ratios of Fcγ receptor blocker for 2 h followed by exposure to PKH-26-labeled RBCs from healthy donors (<italic>n</italic>
 = 5) or from patients with HIV with a positive direct antiglobulin test (DAT) result (<italic>n</italic>
 = 5) or to sRBCs for another 6 h. Healthy RBCs without sensitization were used as a control. The rate of erythrophagocytosis was quantified by flow cytometry. The data represent means ± standard deviations and are representative of results from at least three independent experiments. *<italic>*</italic>
, <italic>P</italic>
 < 0.01; ***, <italic>P < </italic>
0.001; ****, <italic>P < </italic>
0.0001.</p>
</caption>
<graphic xlink:href="mBio.03246-19-f0002"></graphic>
</fig>
<supplementary-material content-type="local-data" id="figS2"><object-id pub-id-type="doi">10.1128/mBio.03246-19.2</object-id>
<label>FIG S2</label>
<p>The C1qR complement receptor is not involved in autoantibody-mediated erythrophagocytosis. (A and B) PMA-differentiated THP-1 macrophages were treated with the indicated dilution ratios of anti-C1q receptor antibody and Fcγ receptor blocker for 2 h followed by incubation with PKH-26-labeled sRBCs for another 6 h as indicated (A), and the rate of erythrophagocytosis was quantified by flow cytometry (B). FSC, forward scatter. ****, <italic>P < </italic>
0.0001. Download <inline-supplementary-material id="fS2" mimetype="image" mime-subtype="tif" xlink:href="mBio.03246-19-sf002.tif" content-type="local-data">FIG S2, TIF file, 1.9 MB</inline-supplementary-material>
.</p>
<permissions><copyright-statement>Copyright © 2020 Dai et al.</copyright-statement>
<copyright-year>2020</copyright-year>
<copyright-holder>Dai et al.</copyright-holder>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><license-p>This content is distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link>
.</license-p>
</license>
</permissions>
</supplementary-material>
</sec>
<sec id="s2.3"><title>Enhanced erythrophagocytosis impairs macrophage bactericidal activity against <named-content content-type="genus-species">M. tuberculosis</named-content>
 by inhibiting autophagy.</title>
<p>Our findings that anti-RBC autoantibodies are an independent risk factor for TB in patients with HIV and that they have a direct effect on erythrophagocytosis prompted us to investigate whether and how erythrophagocytosis influences macrophage-mediated immunity against <named-content content-type="genus-species">M. tuberculosis</named-content>
 infection. We found that erythrophagocytosis significantly impaired the bactericidal activity of PMA-differentiated THP-1 macrophages against <named-content content-type="genus-species">M. tuberculosis</named-content>
 H37Ra (<xref ref-type="fig" rid="fig3">Fig. 3A</xref>
). Specifically, compared to unsensitized RBC treatment and controls, treatment with sRBCs significantly increased intracellular H37Ra growth (<xref ref-type="fig" rid="fig3">Fig. 3A</xref>
). Similar results were obtained when the virulent <named-content content-type="genus-species">M. tuberculosis</named-content>
 H37Rv strain was used to infect primary human monocyte-derived macrophages (hMDMs) (<xref ref-type="fig" rid="fig3">Fig. 3B</xref>
).</p>
<fig id="fig3" orientation="portrait" position="float"><label>FIG 3</label>
<caption><p>Enhanced erythrophagocytosis increases intracellular <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>
 growth. (A) PMA-differentiated THP-1 macrophages were infected with H37Ra (MOI = 10:1) for 6 h. The cells were then treated with unsensitized RBCs or sensitized RBCs (sRBCs) (anti-human RBC IgG, 1,500 μg/ml) at an R/M ratio of 100:1 for 72 h. Macrophage bactericidal activity was assessed by CFU counts of intracellular H37Ra. The data represent means ± standard deviations and are representative of results from at least three independent experiments. (B) Adherent monocytes enriched from PBMCs (from five healthy donors) were allowed to differentiate into human monocyte-derived macrophages (hMDMs) under conditions of stimulation (50 ng/ml macrophage colony-stimulating factor [M-CSF]) in culture. Intracellular CFU levels in hMDMs were assessed for live virulent <named-content content-type="genus-species">M. tuberculosis</named-content>
 as described for panel A. *<italic>*</italic>
, <italic>P < </italic>
0.01.</p>
</caption>
<graphic xlink:href="mBio.03246-19-f0003"></graphic>
</fig>
<p>We then explored the mechanisms by which erythrophagocytosis enhances <named-content content-type="genus-species">M. tuberculosis</named-content>
 intracellular survival. Because heme/iron metabolism and homeostasis following erythrophagocytosis require active phagolysosome biogenesis, involving the interactions of nascent phagosomes with endocytic and autophagy compartments (<xref rid="B24" ref-type="bibr">24</xref>
), we first investigated whether phagosome maturation is affected by sRBCs. The results showed that the pH value of phagosome did not significantly change with or without sRBC treatment in H37Ra-infected macrophages (<xref ref-type="supplementary-material" rid="figS3">Fig. S3</xref>
), suggesting that phagosome maturation is not affected by sRBC treatment. We then focused our study on the role of autophagy in erythrophagocytosis-mediated impairment in bacterial control. We used THP-1 cells transfected with the mRFP-GFP-LC3B (monomeric red fluorescent protein-green fluorescent protein-LC3B) reporter (<xref rid="B25" ref-type="bibr">25</xref>
), a gold standard system for measuring autophagy and monitoring the rate of autophagic flux and the maturation of autophagosomes simultaneously, to evaluate the effect of erythrophagocytosis on autophagy (<xref rid="B26" ref-type="bibr">26</xref>
). Using this system, when autophagosomes mature and fuse with lysosomes to form autolysosomes, GFP degrades in the acidic environment of autolysosomes, whereas mRFP is stable. Therefore, the presence of yellow puncta indicates autophagosome formation (or autophagic flux), and the presence of red puncta indicates autophagosome maturation and the formation of autolysosomes (<xref rid="B27" ref-type="bibr">27</xref>
). Infection with H37Ra and treatment with the autophagy inducer rapamycin induced almost equal levels of autophagosome formation and maturation; conversely, treatment with sRBCs led to a reduction in autophagic flux (<xref ref-type="fig" rid="fig4">Fig. 4A</xref>
 to <xref ref-type="fig" rid="fig4">D</xref>
). This result was confirmed by Western blot analysis of the lipidated and autophagosome-associated LC3B-II form of LC3B (<xref ref-type="fig" rid="fig4">Fig. 4E</xref>
). We further used chloroquine and bafilomycin A1, potent inhibitors of autophagosome-lysosome fusion and acidification, to determine whether the reduction of LC3B-II in the sRBC treatment group was due to an increase in autophagy flux. As expected, both chloroquine and bafilomycin A1 promoted the accumulation of LC3B-II induced by <named-content content-type="genus-species">M. tuberculosis</named-content>
 infection (<xref ref-type="fig" rid="fig4">Fig. 4F</xref>
). These inhibitors did not further increase LC3B-II accumulation in the presence of sRBCs, suggesting that sRBC treatment inhibited autophagy in <named-content content-type="genus-species">M. tuberculosis</named-content>
-infected macrophages (<xref ref-type="fig" rid="fig4">Fig. 4F</xref>
).</p>
<fig id="fig4" orientation="portrait" position="float"><label>FIG 4</label>
<caption><p>Enhanced erythrophagocytosis impairs macrophage bactericidal activity against <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>
 by inhibiting autophagy. (A to D) mRFP-GFP-LC3B reporter THP-1 cells were differentiated by the use of PMA and infected with H37Ra (MOI = 10:1) in the presence or absence of sensitized RBCs (sRBCs) (anti-human RBC IgG, 1,500 μg/ml; R/M ratio = 100:1) for 24 h. Cells treated with 10 nM rapamycin were used as a positive control. (A) Representative confocal microscopy images are shown (bars, 5 μm). (B to D) The number of LC3 puncta (green)/cell (B), the percentage of cells with >5 autolysosomes (red) (C), and the LC3/autolysosome ratio (D) were calculated. (E) PMA-differentiated THP-1 macrophages were infected with H37Ra (MOI = 10:1) for 24 h in the presence or absence of sRBCs at the indicated RBC/macrophage ratios. The lysates from the panel of cells were prepared as described for panel A, and only RBC lysates were analyzed by Western blotting. LC3B-II/histone H3 ratios shown above. (F) PMA-differentiated THP-1 macrophages were infected with H37Ra (MOI = 10:1) for 24 h in the presence or absence of sRBCs (100:1), with or without bafilomycin A1 (100 nM) and chloroquine (25 μM) treatment for another 3 h. The lysates from the panel were analyzed by Western blotting. LC3B-II/histone H3 ratios are shown at the top. DMSO, dimethyl sulfoxide. (G) PMA-differentiated THP-1 macrophages were transfected with <italic>ATG5</italic>
 small interfering RNA (siRNA). Scrambled siRNA was used as a negative control. After 36 h, the cells were infected with H37Ra (MOI = 10:1) for 6 h and then treated with sRBCs (R/M ratio = 100:1) for a further 72 h. The panel of cells was lysed in 0.1% SDS and plated on 7H10 plates for calculating CFU. The data represent means ± standard deviations and are representative of results from at least three independent experiments. <italic>*</italic>
, <italic>P < </italic>
0.05, *<italic>*</italic>
, <italic>P < </italic>
0.01; ***, <italic>P < </italic>
0.001; ****, <italic>P < </italic>
0.0001.</p>
</caption>
<graphic xlink:href="mBio.03246-19-f0004"></graphic>
</fig>
<supplementary-material content-type="local-data" id="figS3"><object-id pub-id-type="doi">10.1128/mBio.03246-19.3</object-id>
<label>FIG S3</label>
<p>Phagosome maturation of H37Ra-infected macrophages is unaffected by sRBC treatment. (A and B) PMA-differentiated THP-1 macrophages were infected with H37Ra (MOI = 10:1) in the presence or absence of sRBCs (R/M ratio = 100:1) for 24 h. pHrodo Red BioParticles were used to detect the pH within phagosomes by flow cytometry. Download <inline-supplementary-material id="fS3" mimetype="image" mime-subtype="tif" xlink:href="mBio.03246-19-sf003.tif" content-type="local-data">FIG S3, TIF file, 1.3 MB</inline-supplementary-material>
.</p>
<permissions><copyright-statement>Copyright © 2020 Dai et al.</copyright-statement>
<copyright-year>2020</copyright-year>
<copyright-holder>Dai et al.</copyright-holder>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><license-p>This content is distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link>
.</license-p>
</license>
</permissions>
</supplementary-material>
<p>To further confirm the inhibition of autophagy by erythrophagocytosis in intracellular <named-content content-type="genus-species">M. tuberculosis</named-content>
 growth, we used small interfering RNA (siRNA) to silence a key autophagy-related gene, <italic>ATG5</italic>
, to interfere with autophagy progression. <italic>ATG5</italic>
 siRNA transfection markedly decreased <italic>ATG5</italic>
 gene expression but had no effect on RBC and <named-content content-type="genus-species">M. tuberculosis</named-content>
 phagocytosis by macrophages (<xref ref-type="supplementary-material" rid="figS4">Fig. S4</xref>
). Consistent with a previous report (<xref rid="B28" ref-type="bibr">28</xref>
), we observed that <italic>ATG5</italic>
 knockdown increased the survival of intracellular <named-content content-type="genus-species">M. tuberculosis</named-content>
; however, unlike control siRNA treatment, the intracellular <named-content content-type="genus-species">M. tuberculosis</named-content>
 CFU count in the <italic>ATG5</italic>
 knockdown macrophages did not increase upon sRBC exposure (<xref ref-type="fig" rid="fig4">Fig. 4G</xref>
). These results indicate that enhanced erythrophagocytosis impairs macrophage bactericidal activity by inhibiting autophagy.</p>
<supplementary-material content-type="local-data" id="figS4"><object-id pub-id-type="doi">10.1128/mBio.03246-19.4</object-id>
<label>FIG S4</label>
<p><italic>ATG5</italic>
 and <italic>HMOX-1</italic>
 knockdown has no effect on macrophage-mediated phagocytosis of sensitized RBCs and <named-content content-type="genus-species">M. tuberculosis</named-content>
. PMA-differentiated THP-1 macrophages were transfected with <italic>ATG5</italic>
 and <italic>HMOX-1</italic>
 siRNA (50 nM). Scrambled siRNA was used as a negative control. (A) Relative expression levels of <italic>ATG5</italic>
 were detected by quantitative PCR (qPCR). (B and C) <italic>In vitro</italic>
 phagocytosis of PKH-26-labeled RBCs after incubation for 6 h with silenced THP-1 macrophages at an RBC/macrophage ratio of 100:1. Data shown were quantified by flow cytometry. (D) <italic>ATG5</italic>
 and <italic>HMOX-1</italic>
 knockdown THP-1 macrophages were infected with H37Ra (MOI = 10:1) for 6 h before calculating levels of intracellular CFUs. The data represent means ± standard deviations and are representative of results from at least three independent experiments. **, <italic>P < </italic>
0.01. Download <inline-supplementary-material id="fS4" mimetype="image" mime-subtype="tif" xlink:href="mBio.03246-19-sf004.tif" content-type="local-data">FIG S4, TIF file, 2.6 MB</inline-supplementary-material>
.</p>
<permissions><copyright-statement>Copyright © 2020 Dai et al.</copyright-statement>
<copyright-year>2020</copyright-year>
<copyright-holder>Dai et al.</copyright-holder>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><license-p>This content is distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link>
.</license-p>
</license>
</permissions>
</supplementary-material>
</sec>
<sec id="s2.4"><title>Erythrophagocytosis inhibits macrophage-mediated autophagy via heme oxygenase-1 (HO-1) expression.</title>
<p>Increased RBC damage or intravascular hemolysis can lead to acute heme accumulation in macrophages (<xref rid="B29" ref-type="bibr">29</xref>
). In response, macrophages promptly upregulate a number of protective mechanisms: these protective responses involve heme catabolism by HO-1 and iron sequestration by ferritin (<xref rid="B29" ref-type="bibr">29</xref>
, <xref rid="B30" ref-type="bibr">30</xref>
). We thus performed RNA sequencing (RNA-seq) to profile the transcriptomes of macrophages infected with H37Ra in the absence or presence of sRBCs. We found that genes directly associated with heme degradation were expressed at higher levels in H37Ra-infected macrophages treated with sRBCs for 12 h than i those without sRBC exposure, including ferritin light chain (<italic>FTL</italic>
), ferritin heavy chain 1 (<italic>FTH1</italic>
), hemoglobin subunit alpha 1/2 (<italic>HBA1</italic>
/<italic>2</italic>
), hemoglobin subunit beta (<italic>HBB</italic>
), and heme oxygenase-1 (<italic>HMOX-1</italic>
) (<xref ref-type="fig" rid="fig5">Fig. 5A</xref>
; see also <xref ref-type="supplementary-material" rid="figS5">Fig. S5</xref>
). Among them, <italic>HMOX-1</italic>
 was differentially expressed at all indicated time points, including 2, 6, 12, and 24 h (<xref ref-type="supplementary-material" rid="figS5">Fig. S5</xref>
). We confirmed a time-dependent expression pattern for HO-1 and FTH by Western blotting and found that the increased expression coincided with the reduced LC3B-II expression (<xref ref-type="fig" rid="fig5">Fig. 5B</xref>
).</p>
<fig id="fig5" orientation="portrait" position="float"><label>FIG 5</label>
<caption><p>Erythrophagocytosis inhibits macrophage autophagy via regulating heme oxygenase-1 (HO-1) expression. (A) PMA-differentiated THP-1 macrophages were infected with H37Ra (MOI = 10:1) in the presence or absence of sensitized RBCs (sRBCs) (anti-human RBC IgG, 1,500 μg/ml; R/M ratio = 100:1) for 2, 6, 12, and 24 h. Total RNA was extracted for library construction and sequencing. The heat map shows the top 15 differentially expressed genes (DEGs) (selected on the basis of an adjusted <italic>P</italic>
 value of <italic><</italic>
0.05 and fold changes of FPKM) in comparisons of H37Ra-infected macrophages treated with or without sRBCs for 12 h. Blue, low expression; red, high expression. The genes differentially expressed at all time points (2, 6, 12, and 24 h) are marked in red. (B) PMA-differentiated THP-1 macrophages were infected with H37Ra (MOI = 10:1) in the presence or absence of sRBCs (R/M ratio = 100:1) for the indicated times. HO-1, ferritin heavy chain (FTH), and LC3B protein levels were examined by Western blotting. (C and E) Expression of HO-1 was monitored in macrophages exposed to the pharmacological inhibitor ZnPPIX (2.5 μM) or DMSO (C) or to specific control siRNA or <italic>HMOX-1</italic>
 siRNA (50 nM) (E) after infection with H37Ra in the presence or absence of sRBCs for 24 h. LC3B protein levels were examined by Western blotting. (D and F) Intracellular H37Ra CFU levels were assessed in macrophages prepared as described for panels C and E followed by sRBC treatment for 72 h. (G) TPH-1 macrophages with <italic>ATG5</italic>
 knockdown were infected with H37Ra (MOI = 10:1) in the presence or absence of sRBCs (R/M ratio = 100:1) for 24 h. HO-1 and LC3B protein levels were examined by Western blotting. (H) PMA-differentiated THP-1 macrophages were infected with H37Ra (MOI = 10:1) in the presence or absence of ferrous lactate (200 μM) for the indicated times. HO-1, FTH, and LC3B protein levels were examined by Western blotting. HO-1 and LC3B-II/histone H3 ratios are shown at the top. The data represent means ± standard deviations and are representative of results from at least three independent experiments. <italic>*</italic>
, <italic>P < </italic>
0.05; *<italic>*</italic>
, <italic>P < </italic>
0.01; ***, <italic>P < </italic>
0.001; ****, <italic>P < </italic>
0.0001.</p>
</caption>
<graphic xlink:href="mBio.03246-19-f0005"></graphic>
</fig>
<supplementary-material content-type="local-data" id="figS5"><object-id pub-id-type="doi">10.1128/mBio.03246-19.5</object-id>
<label>FIG S5</label>
<p>Differentially expressed genes (DEGs) from comparisons between H37Ra-infected THP-1 cells treated with or without sensitized RBCs. PMA-differentiated THP-1 macrophages were infected with H37Ra (MOI = 10:1) in the presence or absence of sensitized RBCs (sRBCs) (anti-human RBC IgG was used at 1,500 μg/ml; R/M ratio = 100:1) for 2, 6, 12, and 24 h. Total RNA was extracted for library construction and sequencing. (A) The top 15 DEGs from comparisons between H37Ra-infected macrophages treated with or without sRBCs for 12 h. (B to P) The expression level of the 15 genes referred to above at different time points (2, 6, 12, and 24 h) in H37Ra-infected macrophages treated with or without sRBCs (red indicates genes identified in the presence of sRBCs). (Q) Venn diagram of the DEGs identified by RNA sequencing in H37Ra-infected macrophages treated with or without sRBCs. Download <inline-supplementary-material id="fS5" mimetype="image" mime-subtype="tif" xlink:href="mBio.03246-19-sf005.tif" content-type="local-data">FIG S5, TIF file, 2.8 MB</inline-supplementary-material>
.</p>
<permissions><copyright-statement>Copyright © 2020 Dai et al.</copyright-statement>
<copyright-year>2020</copyright-year>
<copyright-holder>Dai et al.</copyright-holder>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><license-p>This content is distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link>
.</license-p>
</license>
</permissions>
</supplementary-material>
<p>As HO-1 regulates autophagy (<xref rid="B31" ref-type="bibr">31</xref>
, <xref rid="B32" ref-type="bibr">32</xref>
), we hypothesized that erythrophagocytosis might inhibit autophagy by inducing HO-1 expression. To test this hypothesis, we infected PMA-differentiated THP-1 macrophages with H37Ra and then exposed them to the HO-1 inhibitor zinc protoporphyrin (ZnPPIX; 2.5 μM) and to sRBCs for 24 h. Western blot analysis showed that ZnPPIX treatment partly relieved the inhibitory effect of erythrophagocytosis on LC3B-II expression (<xref ref-type="fig" rid="fig5">Fig. 5C</xref>
). Importantly, we found that ZnPPIX exposure inhibited intracellular bacterial growth compared with the noninhibitor control group; this defect was not rescued by sRBC treatment (<xref ref-type="fig" rid="fig5">Fig. 5D</xref>
).</p>
<p>Exposure to HO-1 inhibitors leads to cellular toxicity due to the production of reactive oxygen species (ROS) in the specific context of photochemical activation (<xref rid="B27" ref-type="bibr">27</xref>
, <xref rid="B33" ref-type="bibr">33</xref>
). Treating H37Ra-infected macrophages with ZnPPIX, however, did not increase cytosolic reactive oxygen species (cROS) production. Rather, it actually decreased the cROS level (<xref ref-type="supplementary-material" rid="figS6">Fig. S6</xref>
). To exclude the possibility of direct bactericidal activity (data not shown) and cellular toxicity induced by ZnPPIX, we therefore used <italic>HMOX-1</italic>
 siRNA to specifically verify the role of HO-1 in inhibiting autophagy during erythrophagocytosis. Transfection with <italic>HMOX-1</italic>
 siRNA markedly decreased the HO-1 protein level in macrophages (<xref ref-type="fig" rid="fig5">Fig. 5E</xref>
) without affecting sRBC and <named-content content-type="genus-species">M. tuberculosis</named-content>
 phagocytosis (<xref ref-type="supplementary-material" rid="figS4">Fig. S4</xref>
) and cell deaths (<xref ref-type="supplementary-material" rid="figS7">Fig. S7</xref>
). Consistent with the effects of ZnPPIX, we found that <italic>HMOX-1</italic>
 knockdown in H37Ra-infected macrophages significantly abrogated the inhibitory effect of erythrophagocytosis on the expression of LC3B-II (<xref ref-type="fig" rid="fig5">Fig. 5E</xref>
). In contrast, impaired autophagy driven by <italic>ATG5</italic>
 silencing had no effect on HO-1 expression (<xref ref-type="fig" rid="fig5">Fig. 5G</xref>
). Most importantly, in accordance with our chemical inhibitor results (<xref ref-type="fig" rid="fig5">Fig. 5E</xref>
) and with a previous report (<xref rid="B34" ref-type="bibr">34</xref>
), <italic>HMOX-1</italic>
 knockdown completely eradicated the inhibitory effects of erythrophagocytosis on the macrophage defense against <named-content content-type="genus-species">M. tuberculosis</named-content>
, as determined by the CFU count of intracellular <named-content content-type="genus-species">M. tuberculosis</named-content>
 (<xref ref-type="fig" rid="fig5">Fig. 5F</xref>
). Taken together, these findings confirm that the increased level of intracellular <named-content content-type="genus-species">M. tuberculosis</named-content>
 survival in response to erythrophagocytosis depends on the inhibition of HO-1-regulated autophagy.</p>
<supplementary-material content-type="local-data" id="figS6"><object-id pub-id-type="doi">10.1128/mBio.03246-19.6</object-id>
<label>FIG S6</label>
<p>ZnPPIX treatment decreases cROS production in <named-content content-type="genus-species">M. tuberculosis</named-content>
-infected macrophages. (A and B) PMA-differentiated THP-1 macrophages were infected with H37Ra (MOI = 10:1) in the presence (A) or absence (B) of ZnPPIX (2.5 μM). cROS production was determined by flow cytometry. ****, <italic>P < </italic>
0.0001. Download <inline-supplementary-material id="fS6" mimetype="image" mime-subtype="tif" xlink:href="mBio.03246-19-sf006.tif" content-type="local-data">FIG S6, TIF file, 0.7 MB</inline-supplementary-material>
.</p>
<permissions><copyright-statement>Copyright © 2020 Dai et al.</copyright-statement>
<copyright-year>2020</copyright-year>
<copyright-holder>Dai et al.</copyright-holder>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><license-p>This content is distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link>
.</license-p>
</license>
</permissions>
</supplementary-material>
<supplementary-material content-type="local-data" id="figS7"><object-id pub-id-type="doi">10.1128/mBio.03246-19.7</object-id>
<label>FIG S7</label>
<p><italic>HMOX-1</italic>
 knockdown has no effect on cell death of macrophages infected with <named-content content-type="genus-species">M. tuberculosis</named-content>
. PMA-differentiated THP-1 macrophages were transfected with <italic>HMOX-1</italic>
 siRNA (50 nM). Scrambled siRNA was used as a negative control. (A and B) Cell deaths were determined using an annexin V/propidium iodide (PI) kit after H37Ra infection (MOI = 10:1) for 24 h by flow cytometry. Download <inline-supplementary-material id="fS7" mimetype="image" mime-subtype="tif" xlink:href="mBio.03246-19-sf007.tif" content-type="local-data">FIG S7, TIF file, 1.6 MB</inline-supplementary-material>
.</p>
<permissions><copyright-statement>Copyright © 2020 Dai et al.</copyright-statement>
<copyright-year>2020</copyright-year>
<copyright-holder>Dai et al.</copyright-holder>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><license-p>This content is distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link>
.</license-p>
</license>
</permissions>
</supplementary-material>
<p>As previously described (<xref rid="B35" ref-type="bibr">35</xref>
), erythrophagocytosis also leads to an increase in iron levels, which might benefit intracellular <named-content content-type="genus-species">M. tuberculosis</named-content>
 growth by compensatory iron acquisition. In our final assays, we found that treating H37Ra-infected macrophages with ferrous lactate (200 μM) neither increased HO-1 levels nor suppressed LC3B-II levels (<xref ref-type="fig" rid="fig5">Fig. 5H</xref>
). As blocking HO-1 completely reversed the inhibitory effects caused by erythrophagocytosis, we reason that erythrophagocytosis supports <named-content content-type="genus-species">M. tuberculosis</named-content>
 intracellular survival by inhibiting autophagy rather than depending fully on heme-iron acquisition.</p>
</sec>
</sec>
<sec sec-type="discussion" id="s3"><title>DISCUSSION</title>
<p>CD4 T-cell depletion has long been considered an important risk factor for TB in HIV. Although the details of the mechanism remain uncertain, recent data have emerged to show that HIV infection may compromise macrophage function to impair host control of <named-content content-type="genus-species">M. tuberculosis</named-content>
 (<xref rid="B2" ref-type="bibr">2</xref>
, <xref rid="B10" ref-type="bibr">10</xref>
, <xref rid="B36" ref-type="bibr">36</xref>
, <xref rid="B37" ref-type="bibr">37</xref>
). To the best of our knowledge, we report for the first time that increased TB susceptibility is significantly associated with anti-RBC autoantibody production (as determined by DAT) in patients with HIV. Enhanced erythrophagocytosis of RBCs by macrophages in DAT-positive patients significantly correlated with anti-RBC autoantibody production and was efficiently blocked with inhibition of Fcγ receptors rather than complement receptors. The erythrophagocytosis of RBCs sensitized with anti-human RBCs IgG induced excessive expression of HO-1, which inhibited autophagy and impaired macrophage bactericidal activity against <named-content content-type="genus-species">M. tuberculosis</named-content>
. These findings provide novel insights into how HIV infection increases TB susceptibility by impairing macrophage anti-TB immunity.</p>
<p>HIV infection induces autoantibody production via mechanisms such as (i) direct B-cell activation as a result of antigen similarity and (ii) dysregulated B-cell activation due to CD4 T-cell depletion (<xref rid="B14" ref-type="bibr">14</xref>
, <xref rid="B38" ref-type="bibr">38</xref>
). Anti-RBC autoantibodies, which sensitize RBCs for destruction, have also been implicated in HIV-associated autoimmune hemolytic anemia (<xref rid="B39" ref-type="bibr">39</xref>
, <xref rid="B40" ref-type="bibr">40</xref>
). A positive DAT result and anemia are frequently observed in the clinical syndrome of HIV infection, and these two parameters are significantly associated with each other (<xref rid="B16" ref-type="bibr">16</xref>
, <xref rid="B22" ref-type="bibr">22</xref>
). Additionally, the severity of anemia can be used to predict the incidence of and mortality associated with TB in patients with HIV (<xref rid="B21" ref-type="bibr">21</xref>
). Consistently, our univariate analysis showed that the rate of anemia was significantly associated with TB incidence in patients with HIV; however, this association was lost in a multivariate analysis. While we saw no significant association between TB incidence and the number of CD4 T cells—possibly because all HIV patients recruited to this study were at an early clinical stage and still had a relatively high level of CD4 T cells—we discovered a strong association between a positive DAT result and the incidence of TB. As the antiviral drugs used for HIV treatment have the potential to induce drug-associated RBC hemolysis and present false-positive DAT results (<xref rid="B20" ref-type="bibr">20</xref>
), we recruited only treatment-naive patients with HIV in the present study to avoid the potentially confounding factor of drug use. Taken together, our data show that anti-RBC autoantibody production is an independent risk factor for TB susceptibility in patients with HIV, regardless of the presence of anemia.</p>
<p><named-content content-type="genus-species">M. tuberculosis</named-content>
 has evolved a highly efficient iron-acquiring system to compete for iron, particularly within extremely hostile environments such as within macrophages (<xref rid="B35" ref-type="bibr">35</xref>
, <xref rid="B41" ref-type="bibr">41</xref>
, <xref rid="B42" ref-type="bibr">42</xref>
). Although we cannot entirely rule out the contribution of heme as an iron source for increased intracellular <named-content content-type="genus-species">M. tuberculosis</named-content>
 growth caused by enhanced erythrophagocytosis, disruption of the autophagic response, by targeting either HO-1 or <italic>ATG5</italic>
, completely abrogated the effects of erythrophagocytosis on macrophagic bactericidal activity against <named-content content-type="genus-species">M. tuberculosis</named-content>
. In addition, treatment with iron (ferrous lactate) did not increase the expression of HO-1 or inhibit autophagy in <named-content content-type="genus-species">M. tuberculosis</named-content>
-infected macrophages. Together, these data suggest that the contribution of iron to increased intracellular <named-content content-type="genus-species">M. tuberculosis</named-content>
 growth during erythrophagocytosis is limited. Further investigations using an <named-content content-type="genus-species">M. tuberculosis</named-content>
 mutant with deficient heme iron uptake systems may provide direct evidence as to whether iron from RBCs serves as a nutrient that is beneficial to intracellular <named-content content-type="genus-species">M. tuberculosis</named-content>
.</p>
<p>HO-1, encoded by <italic>HMOX-1</italic>
, is an inducible cytoprotective enzyme that catalyzes the oxidative degradation of heme into equimolar ratios of iron, carbon monoxide, and bilirubin (<xref rid="B43" ref-type="bibr">43</xref>
). Although the transcript, protein, and activity levels of HO-1 are upregulated in response to <named-content content-type="genus-species">M. tuberculosis</named-content>
 infection, whether HO-1 has a protective or pathogenic role in TB remains controversial (<xref rid="B17" ref-type="bibr">17</xref>
, <xref rid="B34" ref-type="bibr">34</xref>
, <xref rid="B44" ref-type="bibr">44</xref>
<xref ref-type="bibr" rid="B45">–</xref>
<xref rid="B47" ref-type="bibr">47</xref>
). In support of our findings, several reports have shown that pharmacological HO-1 inhibition decreases <named-content content-type="genus-species">M. tuberculosis</named-content>
 and <named-content content-type="genus-species">Mycobacterium abscessus</named-content>
 burden <italic>in vivo</italic>
 (<xref rid="B44" ref-type="bibr">44</xref>
) and <italic>in vitro</italic>
 (<xref rid="B34" ref-type="bibr">34</xref>
, <xref rid="B45" ref-type="bibr">45</xref>
). Conversely, others have shown that HO-1 is required to control <named-content content-type="genus-species">M. tuberculosis</named-content>
 and <named-content content-type="genus-species">Mycobacterium avium</named-content>
 infections in mice (<xref rid="B17" ref-type="bibr">17</xref>
, <xref rid="B46" ref-type="bibr">46</xref>
, <xref rid="B47" ref-type="bibr">47</xref>
). These conflicting findings might be due to the off-target effects of HO-1 chemical inhibitors and to the fact that the essentiality of HO-1 in mice and humans varies; however, it should be highlighted that the roles of HO-1 in restricting <named-content content-type="genus-species">M. tuberculosis</named-content>
 infection may diverge under different circumstances in a manner that depends on the dynamics of HO-1 expression. During normal RBC homeostasis, the expression and enzyme activity of HO-1 is induced but is tightly regulated to counteract oxidative stress or heme, with the purpose to protect macrophages from death, and therefore benefits the host defense against TB. However, under circumstances such as enhanced erythrophagocytosis in patients with HIV, expression of excessive HO-1 is induced and sustained, which inhibits autophagy and thus facilitates intracellular <named-content content-type="genus-species">M. tuberculosis</named-content>
 growth (<xref rid="B47" ref-type="bibr">47</xref>
). In agreement with previous reports (<xref rid="B48" ref-type="bibr">48</xref>
), we found that HO-1 was significantly upregulated in macrophages at an early time point (∼6 h) after <named-content content-type="genus-species">M. tuberculosis</named-content>
 infection. HO-1 expression, however, decreased at a late time point (∼12 h) following infection. Notably, erythrophagocytosis not only significantly increased the <named-content content-type="genus-species">M. tuberculosis</named-content>
 infection-induced upregulation of HO-1 but also sustained its expression up to 24 h after infection.</p>
<p>A similar phenomenon is the role of HO-1 in the modulation of autophagy. Depending on the cell type and stressor, HO-1 can inhibit or induce autophagy in a signal-specific and cell line-specific manner. For example, induction of autophagy is dependent on HO-1 in primary mouse macrophages and hepatocytes (<xref rid="B49" ref-type="bibr">49</xref>
, <xref rid="B50" ref-type="bibr">50</xref>
). In lung and colon cancer, HO-1-mediated autophagy sustains cancer cell survival and leads to a more aggressive phenotype (<xref rid="B51" ref-type="bibr">51</xref>
, <xref rid="B52" ref-type="bibr">52</xref>
). Conversely, recent studies have shown that HO-1 may also inhibit autophagy to protect renal tubules from cisplatin-mediated injury (<xref rid="B31" ref-type="bibr">31</xref>
) and modulate hyperthermia-induced antiviral effects in cervical cancer cells (<xref rid="B32" ref-type="bibr">32</xref>
). We believe, therefore, that it is important to further address the reasons underlying the paradoxical effects of HO-1 on control of <named-content content-type="genus-species">M. tuberculosis</named-content>
 infection and regulating autophagy. Nevertheless, our study results confirm that HO-1 induction by anti-RBC autoantibody-mediated erythrophagocytosis is essential and sufficient to impair macrophage bactericidal activity against <named-content content-type="genus-species">M. tuberculosis</named-content>
 by inhibiting <italic>ATG5</italic>
-dependent autophagy by applying pharmacological inhibitors of HO-1 and knocking down HO-1 with siRNA.</p>
<p>In summary, we have shown that HIV infection increases autoantibody-mediated erythrophagocytosis, which impairs macrophagic bactericidal activity against <named-content content-type="genus-species">M. tuberculosis</named-content>
 by inhibiting HO-1-associated autophagy. These findings reveal a novel mechanism by which HIV infection increases susceptibility to TB and provide evidence that DAT could be a potential measure to identify HIV patients who are at high risk of TB and who thus would be suitable candidates for anti-TB chemotherapy preventive treatment.</p>
</sec>
<sec sec-type="materials|methods" id="s4"><title>MATERIALS AND METHODS</title>
<sec id="s4.1"><title>Ethics statement.</title>
<p>The present study was approved by the Ethics Committees of the Shenzhen Third Hospital (Shenzhen, China). Written informed consent was provided by all study participants.</p>
</sec>
<sec id="s4.2"><title>Study population and samples.</title>
<p>To investigate the presence of red blood cell (RBC) autoantibodies in patients with HIV and its association with the susceptibility to tuberculosis (TB), 281 HIV-seropositive patients were recruited from the Shenzhen Third Hospital (Shenzhen, China) between August 2017 and November 2018. All participants underwent clinical assessment at recruitment, and information was collected on age, sex, HIV copy numbers, hemoglobin level, white blood cell (WBC) count, CD4 T-cell count, direct antiglobulin test (DAT) result, and results from examinations conducted for diagnosing TB, such as chest radiography, interferon gamma release assay (IGRA), and sputum microbiological tests, including acid-fast bacillus (AFB) staining, nucleic acid amplification test (NAAT), and <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>
 culture. Among the potential subjects, 14 cases were excluded due to missing data or questionable diagnosis. Subsequently, a total of 267 cases that had a conclusive clinical diagnosis were included in the study. The clinical and demographic data are shown in <xref rid="tab1" ref-type="table">Table 1</xref>
. As described previously (<xref rid="B53" ref-type="bibr">53</xref>
), TB was diagnosed by experienced specialists if (i) sputum samples were positive for AFB, NAAT, or <named-content content-type="genus-species">M. tuberculosis</named-content>
 culture or (ii) the results showed no sputum evidence or a negative smear but did show high-resolution computed tomography evidence, positive IGRA, and symptoms responding to TB treatment.</p>
<p>For erythrophagocytosis analysis, 33 healthy donors and 47 HIV-seropositive patients who were not coinfected with TB (including 36 DAT-negative cases and 11 DAT-positive cases) were selected (see <xref ref-type="supplementary-material" rid="tabS1">Table S1</xref>
 in the supplemental material). Here, 5 ml whole blood was collected for RBC and human peripheral blood mononuclear cell (PBMC) isolation and 5 ml for DAT by venipuncture, using heparinized tubes and ethylenediaminetetraacetic acid (EDTA) tubes (Sigma), respectively.</p>
</sec>
<sec id="s4.3"><title>Cell isolation and culture.</title>
<p>Human monocytic THP-1 (TIB-202; ATCC) cells and THP-1 cells transformed with an mRFP-GFP-LC3B reporter (provided by Hongbo Shen, Institute Pasteur of Shanghai, Shanghai, China) were grown in RPMI 1640 medium supplemented with <sc>l</sc>
-glutamine (2 mM) and 10% heat-inactivated fetal bovine serum (FBS) (all from Gibco, Life Technologies). As previously described (<xref rid="B54" ref-type="bibr">54</xref>
), the THP-1 cells were plated at 4 × 10<sup>5</sup>
 cells/ml in RPMI 1640 (10% FBS, 2 mM <sc>l</sc>
-glutamine) and treated with 40 ng/ml phorbol 12-myristate 13-acetate (PMA; Sigma-Aldrich) in 12-well or 6-well plates (Costar) for 48 h and allowed to differentiate into macrophages, unless otherwise indicated. The cells were then incubated with fresh prewarmed RPMI 1640 (10% FBS, 2 mM <sc>l</sc>
-glutamine) and maintained in the media at 37°C until further use.</p>
<p>PBMCs were isolated by density gradient centrifugation (400 × <italic>g</italic>
, 30 min) using Ficoll-Paque medium (GE), as previously described (<xref rid="B55" ref-type="bibr">55</xref>
). The PBMCs were then incubated overnight to enrich for monocytes by adherence on plastic culture plates. Nonadherent cells were removed via two washes with prewarmed RPMI 1640, and the adherent monocytes were treated with 50 ng/ml human macrophage colony stimulating factor (PeproTech)–RPMI 1640 (supplemented with 10% FBS and 2 mM <sc>l</sc>
-glutamine) for 5 days to enable differentiation into human monocyte-derived macrophages (hMDMs).</p>
<p>Human fresh RBCs from whole blood were separated by density gradient centrifugation (400 × <italic>g</italic>
, 30 min). Following centrifugation, all layers on RBCs were carefully removed. The sedimented RBCs were washed three times with phosphate-buffered saline (PBS) and then underwent WBC depletion by filtration (Pall) (<xref rid="B56" ref-type="bibr">56</xref>
). The RBCs isolated from patients with HIV and healthy donors were stored in citrate phosphate dextrose buffer (Baxter Healthcare) at 4°C for use within 3 days.</p>
</sec>
<sec id="s4.4"><title>DAT.</title>
<p>The DAT was run using a Grifols DG gel system with Coombs cards and monospecific reagent (all from Grifols Diagnostic Solutions Inc.) to detect bound IgG. The whole blood was anticoagulated with EDTA and then centrifuged (400 × <italic>g</italic>
, 5 min) to separate the cells from the plasma. The sedimented RBCs were washed three times and resuspended in PBS to a final concentration of 1%. Following this, 50 μl 1% RBCs was added to microtubes and centrifuged for 9 min using a preset cycle for antibody identification. The results of reactions were generated automatically through artificial vision technology and evaluated using a scale of strength as follows: negative (-) or increasingly positive at 1+, 2+, 3+, or 4+ (<xref rid="B20" ref-type="bibr">20</xref>
, <xref rid="B57" ref-type="bibr">57</xref>
). The experiment was performed under the supervision of trained and experienced medical technicians.</p>
</sec>
<sec id="s4.5"><title>RBC preparation and erythrophagocytosis assay.</title>
<p>The isolated RBCs were washed three times and then labeled with a membrane-integrating dye (PKH-26) (Sigma), according to the manufacturer’s instructions (<xref rid="B23" ref-type="bibr">23</xref>
). In detail, a 2× cell suspension containing 5 × 10<sup>7</sup>
 RBCs in 1 ml diluent C buffer was prepared and then rapidly mixed with dye solution (2×) containing 4 μl PKH-26 dye in 1 ml diluent C buffer. After incubation for 5 min at room temperature, an equal volume (2 ml) of FBS (Gibco, Life Technologies) was added to stop the staining. The labeled RBCs were washed three times and resuspended in RPMI 1640 for the erythrophagocytosis assay. Prior to labeling, the RBCs were sensitized (if required) by incubating the cells in 25, 375, and 1,500 μg/ml commercial rabbit anti-human RBC IgG (Aviva Systems Biology) or isotype rabbit IgG (Abcam) at room temperature for 30 min and then washed three times and resuspended in diluent C buffer for labeling.</p>
<p>For the erythrophagocytosis assay, the PMA-differentiated THP-1 macrophages were pretreated with or without Fcγ receptor blocker (containing anti-CD16, anti-CD32, and anti-CD64; BioLegend) and anti-C1q receptor antibody (ImmunoWay Biotechnology Company) at dilution ratios of 1:1,000, 1:200, and 1:100 for 2 h and were then treated with PKH-26-labeled RBCs at the indicated RBC/macrophage (R/M) ratios of 10:1 and 100:1 for 0.5, 1, 2, 6, 12, and 24 h. The culture supernatants were then removed, and 1 ml RBC lysis buffer (Solarbio) was added to each well followed by incubation for 5 min at room temperature. The cells were washed once in PBS and collected following trypsin (Gibco, Life Technologies) digestion for 5 min. The macrophage erythrophagocytosis rate was analyzed using flow cytometry (BD FACSAria II) and FlowJo software version 10 (BD).</p>
</sec>
<sec id="s4.6"><title><named-content content-type="genus-species">M. tuberculosis</named-content>
 culture, cell infection, and measurement of CFU.</title>
<p><named-content content-type="genus-species">M. tuberculosis</named-content>
 virulent H37Rv and attenuated H37Ra strains were both cultured in Middlebrook 7H9 medium supplemented with 10% oleic acid-albumin-dextrose-catalase (OADC) enrichment medium (Becton, Dickinson), 0.2% (vol/vol) glycerol (Sigma), and 0.25% (vol/vol) Tween 80 (Sigma) at 37°C, as previously described (<xref rid="B58" ref-type="bibr">58</xref>
). <named-content content-type="genus-species">M. tuberculosis</named-content>
 in mid-log-phase growth was used for infection experiments at an optical density (OD) of 0.6. The OD was correlated with the CFU level after colony counts were performed in triplicate on Middlebrook 7H10 agar supplemented with 10% OADC, 0.5% glycerol, and 1g/liter <sc>l</sc>
-asparagine (Sigma).</p>
<p>The PMA-differentiated THP-1 macrophages and hMDMs were infected with <named-content content-type="genus-species">M. tuberculosis</named-content>
 (multiplicity of infection [MOI] = 10:1) for 6 h and then washed three times. The cells were treated with unsensitized RBCs or sensitized RBCs (sRBCs) (anti-human RBC IgG, 1,500 μg/ml; RBC/macrophage [R/M] ratio = 100:1) for a further 72 h. Macrophage bactericidal activity was assessed by determination of <named-content content-type="genus-species">M. tuberculosis</named-content>
 CFU counts obtained from the intracellular environments. The cells were lysed in 0.1% SDS, and lysates were plated at various dilutions on 7H10 plates, which were incubated at 37°C for 2 to 4 weeks before CFU counting was performed, as previously described (<xref rid="B59" ref-type="bibr">59</xref>
).</p>
</sec>
<sec id="s4.7"><title>Confocal microscopy.</title>
<p>THP-1 cells (1 × 10<sup>5</sup>
 cells/ml) transformed with the mRFP-GFP-LC3B reporter were differentiated by the use of PMA and infected with H37Ra (MOI = 10:1) in the presence or absence of sRBCs (R/M ratio = 100:1) for 24 h. A group treated with 10 nM rapamycin was used as a positive control. The cells were washed twice in PBS and fixed with 4% paraformaldehyde solution (Solarbio) for 15 min, and slides were prepared using antifade (Invitrogen), viewed under a confocal microscope (Nikon A1R), and processed using ImageJ software (NIH, USA). The level of autophagy was measured by enumerating the number of puncta per cell, and cells with >5 autolysosomes per 100 cells were counted.</p>
</sec>
<sec id="s4.8"><title>RNA interference and transfection.</title>
<p><italic>ATG5</italic>
 and <italic>HMOX-1</italic>
 siRNA (RiboBio; siB12531154855-1-5 and siG0931881756-1-5, respectively) transfections were performed as previously described (<xref rid="B60" ref-type="bibr">60</xref>
) using Lipofectamine RNAiMAX (Invitrogen) according to the manufacturer’s protocol. The siRNA and Lipofectamine complexes were prepared in Opti-MEM (Gibco) at a 1:1 ratio and added to the predifferentiated THP-1 macrophages for 24 h in a dropwise manner. The medium was replaced after 36 h, and scrambled siRNA was used as a negative control. HO-1 expression was also inhibited by 2.5 μM zinc protoporphyrin (Sigma) treatment. The efficiency of knockdown was determined in both cases by quantitative reverse transcription-PCR (RT-qPCR) and/or Western blotting.</p>
</sec>
<sec id="s4.9"><title>Western blotting.</title>
<p>Following performance of the treatments as described in a previous study (<xref rid="B61" ref-type="bibr">61</xref>
), cells were washed with PBS and lysed on ice by incubation in radioimmunoprecipitation assay (RIPA) lysis buffer (Cell Signaling Technology) supplemented with a protease inhibitor cocktail (Roche). The protein concentration was estimated on a Qubit 4.0 Fluorometer using a Qubit protein assay kit (Thermo Fisher), and the samples were separated by SDS-PAGE and transferred onto a polyvinylidene difluoride membrane (Merck/Millipore). Following blocking with 5% skim milk (BD)–phosphate-buffered saline with Tween 20 (PBST) for 2 h at room temperature, the membranes were incubated with antibodies against LC3B (Sigma), HO-1, ferritin heavy chain, or histone H3 (obtained from Abcam) overnight at 4°C and were then incubated with peroxidase-conjugated secondary antibodies (Abcam) and visualized using ECL detection solution (Thermo Fisher). The digital images of the protein bands were acquired using an ImageQuant LAS 4000 system (GE Healthcare Bio-Science). The densitometry of the protein bands was analyzed using ImageJ software (NIH, USA).</p>
</sec>
<sec id="s4.10"><title>RNA-seq analysis.</title>
<p>Total RNA was isolated using total RNA kits (Omega) and subjected to cDNA library construction and RNA-seq by the Beijing Genomics Institute. In brief, mRNA sequencing was conducted using a BGISEQ-500 platform and the high-quality reads were aligned to the human reference genome (hg19) with Bowtie 2. The expression levels of each of the genes were normalized to the number of fragments per kilobase per million (FPKM) mapped reads in an exon model by RNA-seq expectation maximization (RSEM). Significantly differentially expressed genes were defined on the basis of a >2-fold expression difference versus the control with an adjusted <italic>P</italic>
 value of <0.05.</p>
</sec>
<sec id="s4.11"><title>Statistical analyses.</title>
<p>Analyses were performed using GraphPad Prism Version 6 (GraphPad Software, Inc.) and SAS Version 9.4 (SAS Institute, Inc.). Univariate and multivariate logistic regression models were used to assess the factors associated with TB susceptibility in patients with HIV. One-way analysis of variance (ANOVA) and Tukey’s correction test were used to analyze differences among multiple groups. An unpaired Student's <italic>t</italic>
 test was used to analyze differences between two groups. A paired Student's <italic>t</italic>
 test was used to analyze the differences in erythrophagocytosis rates between the macrophages incubated with and without Fcγ receptor blocker. A Pearson’s <italic>t</italic>
 test was used to analyze the correlation between the phagocytosis rates of RBCs from patients with HIV and the agglutination degrees from DAT. A <italic>P</italic>
 value of <0.05 was considered statistically significant.</p>
</sec>
</sec>
</body>
<back><fn-group><fn fn-type="other"><p><bold>Citation</bold>
 Dai Y, Cai Y, Wang X, Zhu J, Liu X, Liu H, Li L, Zhang Y, Liu S, Wen Z, Feng CG, Chen X, Tang X. 2020. Autoantibody-mediated erythrophagocytosis increases tuberculosis susceptibility in HIV patients. mBio 11:e03246-19. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/mBio.03246-19">https://doi.org/10.1128/mBio.03246-19</ext-link>
.</p>
</fn>
</fn-group>
<ack><title>ACKNOWLEDGMENTS</title>
<p>We thank Jessica Tamanini (Shenzhen University and ET editing) for editing the manuscript prior to submission and thank all participants and site staff of Shenzhen Third Hospital (Shenzhen, China) and Guangzhou Eighth People’s Hospital (Guangzhou, China) for their contributions to the study. We also thank Hongbo Shen (Institute Pasteur of Shanghai, Shanghai, China) for gifting mRFP-GFP-LC3B THP-1 cells and for assistance in detecting autophagic flux.</p>
<p>This study was supported by the National Science and Technology Major Project of China (grant no. 2017ZX10201301-001-001 and 2017ZX10201301-001-002), the Natural Science Foundation of China (grant no. 81525016/81772145/91942315/81770013/81871255), the Science and Technology Project of Shenzhen (grant no. JCYJ20160427184123851, JCYJ20160427151540695, and JCYJ20170307095303424), and Guangdong Provincial Key Laboratory of Regional Immunity and Diseases (2019B030301009).</p>
<p>The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.</p>
</ack>
<ref-list><title>REFERENCES</title>
<ref id="B1"><label>1.</label>
<mixed-citation publication-type="book"><collab>World Health Organization</collab>
. <year>2018</year>
<article-title>Global tuberculosis report</article-title>
. <publisher-name>World Health Organization</publisher-name>
, <publisher-loc>Geneva, Switzerland</publisher-loc>
.</mixed-citation>
</ref>
<ref id="B2"><label>2.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Bell</surname>
<given-names>LCK</given-names>
</name>
, <name name-style="western"><surname>Noursadeghi</surname>
<given-names>M</given-names>
</name>
</person-group>
<year>2018</year>
<article-title>Pathogenesis of HIV-1 and Mycobacterium tuberculosis co-infection</article-title>
. <source>Nat Rev Microbiol</source>
<volume>16</volume>
:<fpage>80</fpage>
–<lpage>90</lpage>
. doi:<pub-id pub-id-type="doi">10.1038/nrmicro.2017.128</pub-id>
.<pub-id pub-id-type="pmid">29109555</pub-id>
</mixed-citation>
</ref>
<ref id="B3"><label>3.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Getahun</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Gunneberg</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Granich</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Nunn</surname>
<given-names>P</given-names>
</name>
</person-group>
<year>2010</year>
<article-title>HIV infection-associated tuberculosis: the epidemiology and the response</article-title>
. <source>Clin Infect Dis</source>
<volume>50</volume>
(<issue>Suppl 3</issue>
):<fpage>S201</fpage>
–<lpage>S207</lpage>
. doi:<pub-id pub-id-type="doi">10.1086/651492</pub-id>
.<pub-id pub-id-type="pmid">20397949</pub-id>
</mixed-citation>
</ref>
<ref id="B4"><label>4.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Sonnenberg</surname>
<given-names>P</given-names>
</name>
, <name name-style="western"><surname>Glynn</surname>
<given-names>JR</given-names>
</name>
, <name name-style="western"><surname>Fielding</surname>
<given-names>K</given-names>
</name>
, <name name-style="western"><surname>Murray</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Godfrey-Faussett</surname>
<given-names>P</given-names>
</name>
, <name name-style="western"><surname>Shearer</surname>
<given-names>S</given-names>
</name>
</person-group>
<year>2005</year>
<article-title>How soon after infection with HIV does the risk of tuberculosis start to increase? A retrospective cohort study in South African gold miners</article-title>
. <source>J Infect Dis</source>
<volume>191</volume>
:<fpage>150</fpage>
–<lpage>158</lpage>
. doi:<pub-id pub-id-type="doi">10.1086/426827</pub-id>
.<pub-id pub-id-type="pmid">15609223</pub-id>
</mixed-citation>
</ref>
<ref id="B5"><label>5.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kalsdorf</surname>
<given-names>B</given-names>
</name>
, <name name-style="western"><surname>Scriba</surname>
<given-names>TJ</given-names>
</name>
, <name name-style="western"><surname>Wood</surname>
<given-names>K</given-names>
</name>
, <name name-style="western"><surname>Day</surname>
<given-names>CL</given-names>
</name>
, <name name-style="western"><surname>Dheda</surname>
<given-names>K</given-names>
</name>
, <name name-style="western"><surname>Dawson</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Hanekom</surname>
<given-names>WA</given-names>
</name>
, <name name-style="western"><surname>Lange</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Wilkinson</surname>
<given-names>RJ</given-names>
</name>
</person-group>
<year>2009</year>
<article-title>HIV-1 infection impairs the bronchoalveolar T-cell response to mycobacteria</article-title>
. <source>Am J Respir Crit Care Med</source>
<volume>180</volume>
:<fpage>1262</fpage>
–<lpage>1270</lpage>
. doi:<pub-id pub-id-type="doi">10.1164/rccm.200907-1011OC</pub-id>
.<pub-id pub-id-type="pmid">19797156</pub-id>
</mixed-citation>
</ref>
<ref id="B6"><label>6.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Geldmacher</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Ngwenyama</surname>
<given-names>N</given-names>
</name>
, <name name-style="western"><surname>Schuetz</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Petrovas</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Reither</surname>
<given-names>K</given-names>
</name>
, <name name-style="western"><surname>Heeregrave</surname>
<given-names>EJ</given-names>
</name>
, <name name-style="western"><surname>Casazza</surname>
<given-names>JP</given-names>
</name>
, <name name-style="western"><surname>Ambrozak</surname>
<given-names>DR</given-names>
</name>
, <name name-style="western"><surname>Louder</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Ampofo</surname>
<given-names>W</given-names>
</name>
, <name name-style="western"><surname>Pollakis</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Hill</surname>
<given-names>B</given-names>
</name>
, <name name-style="western"><surname>Sanga</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>Saathoff</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>Maboko</surname>
<given-names>L</given-names>
</name>
, <name name-style="western"><surname>Roederer</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Paxton</surname>
<given-names>WA</given-names>
</name>
, <name name-style="western"><surname>Hoelscher</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Koup</surname>
<given-names>RA</given-names>
</name>
</person-group>
<year>2010</year>
<article-title>Preferential infection and depletion of Mycobacterium tuberculosis-specific CD4 T cells after HIV-1 infection</article-title>
. <source>J Exp Med</source>
<volume>207</volume>
:<fpage>2869</fpage>
–<lpage>2881</lpage>
. doi:<pub-id pub-id-type="doi">10.1084/jem.20100090</pub-id>
.<pub-id pub-id-type="pmid">21115690</pub-id>
</mixed-citation>
</ref>
<ref id="B7"><label>7.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Bell</surname>
<given-names>LC</given-names>
</name>
, <name name-style="western"><surname>Pollara</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Pascoe</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Tomlinson</surname>
<given-names>GS</given-names>
</name>
, <name name-style="western"><surname>Lehloenya</surname>
<given-names>RJ</given-names>
</name>
, <name name-style="western"><surname>Roe</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Meldau</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Miller</surname>
<given-names>RF</given-names>
</name>
, <name name-style="western"><surname>Ramsay</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Chain</surname>
<given-names>BM</given-names>
</name>
, <name name-style="western"><surname>Dheda</surname>
<given-names>K</given-names>
</name>
, <name name-style="western"><surname>Noursadeghi</surname>
<given-names>M</given-names>
</name>
</person-group>
<year>2016</year>
<article-title>In vivo molecular dissection of the effects of HIV-1 in active tuberculosis</article-title>
. <source>PLoS Pathog</source>
<volume>12</volume>
:<elocation-id>e1005469</elocation-id>
. doi:<pub-id pub-id-type="doi">10.1371/journal.ppat.1005469</pub-id>
.<pub-id pub-id-type="pmid">26986567</pub-id>
</mixed-citation>
</ref>
<ref id="B8"><label>8.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Esmail</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Riou</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Bruyn</surname>
<given-names>ED</given-names>
</name>
, <name name-style="western"><surname>Lai</surname>
<given-names>RP</given-names>
</name>
, <name name-style="western"><surname>Harley</surname>
<given-names>YXR</given-names>
</name>
, <name name-style="western"><surname>Meintjes</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Wilkinson</surname>
<given-names>KA</given-names>
</name>
, <name name-style="western"><surname>Wilkinson</surname>
<given-names>RJ</given-names>
</name>
</person-group>
<year>2018</year>
<article-title>The immune response to Mycobacterium tuberculosis in HIV-1-coinfected persons</article-title>
. <source>Annu Rev Immunol</source>
<volume>36</volume>
:<fpage>603</fpage>
–<lpage>638</lpage>
. doi:<pub-id pub-id-type="doi">10.1146/annurev-immunol-042617-053420</pub-id>
.<pub-id pub-id-type="pmid">29490165</pub-id>
</mixed-citation>
</ref>
<ref id="B9"><label>9.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Gupta</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Wood</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Kaplan</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Bekker</surname>
<given-names>LG</given-names>
</name>
, <name name-style="western"><surname>Lawn</surname>
<given-names>SD</given-names>
</name>
</person-group>
<year>2012</year>
<article-title>Tuberculosis incidence rates during 8 years of follow-up of an antiretroviral treatment cohort in South Africa: comparison with rates in the community</article-title>
. <source>PLoS One</source>
<volume>7</volume>
:<elocation-id>e34156</elocation-id>
. doi:<pub-id pub-id-type="doi">10.1371/journal.pone.0034156</pub-id>
.<pub-id pub-id-type="pmid">22479548</pub-id>
</mixed-citation>
</ref>
<ref id="B10"><label>10.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Jambo</surname>
<given-names>KC</given-names>
</name>
, <name name-style="western"><surname>Banda</surname>
<given-names>DH</given-names>
</name>
, <name name-style="western"><surname>Kankwatira</surname>
<given-names>AM</given-names>
</name>
, <name name-style="western"><surname>Sukumar</surname>
<given-names>N</given-names>
</name>
, <name name-style="western"><surname>Allain</surname>
<given-names>TJ</given-names>
</name>
, <name name-style="western"><surname>Heyderman</surname>
<given-names>RS</given-names>
</name>
, <name name-style="western"><surname>Russell</surname>
<given-names>DG</given-names>
</name>
, <name name-style="western"><surname>Mwandumba</surname>
<given-names>HC</given-names>
</name>
</person-group>
<year>2014</year>
<article-title>Small alveolar macrophages are infected preferentially by HIV and exhibit impaired phagocytic function</article-title>
. <source>Mucosal Immunol</source>
<volume>7</volume>
:<fpage>1116</fpage>
–<lpage>1126</lpage>
. doi:<pub-id pub-id-type="doi">10.1038/mi.2013.127</pub-id>
.<pub-id pub-id-type="pmid">24472847</pub-id>
</mixed-citation>
</ref>
<ref id="B11"><label>11.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Mlcochova</surname>
<given-names>P</given-names>
</name>
, <name name-style="western"><surname>Sutherland</surname>
<given-names>KA</given-names>
</name>
, <name name-style="western"><surname>Watters</surname>
<given-names>SA</given-names>
</name>
, <name name-style="western"><surname>Bertoli</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>de Bruin</surname>
<given-names>RA</given-names>
</name>
, <name name-style="western"><surname>Rehwinkel</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Neil</surname>
<given-names>SJ</given-names>
</name>
, <name name-style="western"><surname>Lenzi</surname>
<given-names>GM</given-names>
</name>
, <name name-style="western"><surname>Kim</surname>
<given-names>B</given-names>
</name>
, <name name-style="western"><surname>Khwaja</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Gage</surname>
<given-names>MC</given-names>
</name>
, <name name-style="western"><surname>Georgiou</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Chittka</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Yona</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Noursadeghi</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Towers</surname>
<given-names>GJ</given-names>
</name>
, <name name-style="western"><surname>Gupta</surname>
<given-names>RK</given-names>
</name>
</person-group>
<year>2017</year>
<article-title>A G1-like state allows HIV-1 to bypass SAMHD1 restriction in macrophages</article-title>
. <source>EMBO J</source>
<volume>36</volume>
:<fpage>604</fpage>
–<lpage>616</lpage>
. doi:<pub-id pub-id-type="doi">10.15252/embj.201696025</pub-id>
.<pub-id pub-id-type="pmid">28122869</pub-id>
</mixed-citation>
</ref>
<ref id="B12"><label>12.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Nunes-Alves</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Booty</surname>
<given-names>MG</given-names>
</name>
, <name name-style="western"><surname>Carpenter</surname>
<given-names>SM</given-names>
</name>
, <name name-style="western"><surname>Jayaraman</surname>
<given-names>P</given-names>
</name>
, <name name-style="western"><surname>Rothchild</surname>
<given-names>AC</given-names>
</name>
, <name name-style="western"><surname>Behar</surname>
<given-names>SM</given-names>
</name>
</person-group>
<year>2014</year>
<article-title>In search of a new paradigm for protective immunity to TB</article-title>
. <source>Nat Rev Microbiol</source>
<volume>12</volume>
:<fpage>289</fpage>
–<lpage>299</lpage>
. doi:<pub-id pub-id-type="doi">10.1038/nrmicro3230</pub-id>
.<pub-id pub-id-type="pmid">24590243</pub-id>
</mixed-citation>
</ref>
<ref id="B13"><label>13.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Rothchild</surname>
<given-names>AC</given-names>
</name>
, <name name-style="western"><surname>Sissons</surname>
<given-names>JR</given-names>
</name>
, <name name-style="western"><surname>Shafiani</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Plaisier</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Min</surname>
<given-names>D</given-names>
</name>
, <name name-style="western"><surname>Mai</surname>
<given-names>D</given-names>
</name>
, <name name-style="western"><surname>Gilchrist</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Peschon</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Larson</surname>
<given-names>RP</given-names>
</name>
, <name name-style="western"><surname>Bergthaler</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Baliga</surname>
<given-names>NS</given-names>
</name>
, <name name-style="western"><surname>Urdahl</surname>
<given-names>KB</given-names>
</name>
, <name name-style="western"><surname>Aderem</surname>
<given-names>A</given-names>
</name>
</person-group>
<year>2016</year>
<article-title>MiR-155-regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis</article-title>
. <source>Proc Natl Acad Sci U S A</source>
<volume>113</volume>
:<fpage>E6172</fpage>
–<lpage>E6181</lpage>
. doi:<pub-id pub-id-type="doi">10.1073/pnas.1608255113</pub-id>
.<pub-id pub-id-type="pmid">27681624</pub-id>
</mixed-citation>
</ref>
<ref id="B14"><label>14.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Martinez</surname>
<given-names>V</given-names>
</name>
, <name name-style="western"><surname>Diemert</surname>
<given-names>MC</given-names>
</name>
, <name name-style="western"><surname>Braibant</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Potard</surname>
<given-names>V</given-names>
</name>
, <name name-style="western"><surname>Charuel</surname>
<given-names>JL</given-names>
</name>
, <name name-style="western"><surname>Barin</surname>
<given-names>F</given-names>
</name>
, <name name-style="western"><surname>Costagliola</surname>
<given-names>D</given-names>
</name>
, <name name-style="western"><surname>Caumes</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>Clauvel</surname>
<given-names>JP</given-names>
</name>
, <name name-style="western"><surname>Autran</surname>
<given-names>B</given-names>
</name>
, <name name-style="western"><surname>Musset</surname>
<given-names>L</given-names>
</name>
</person-group>
, <collab>ALT ANRS CO15 Study Group</collab>
. <year>2009</year>
<article-title>Anticardiolipin antibodies in HIV infection are independently associated with antibodies to the membrane proximal external region of gp41 and with cell-associated HIV DNA and immune activation</article-title>
. <source>Clin Infect Dis</source>
<volume>48</volume>
:<fpage>123</fpage>
–<lpage>132</lpage>
. doi:<pub-id pub-id-type="doi">10.1086/595013</pub-id>
.<pub-id pub-id-type="pmid">19035778</pub-id>
</mixed-citation>
</ref>
<ref id="B15"><label>15.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>De Angelis</surname>
<given-names>V</given-names>
</name>
, <name name-style="western"><surname>Biasinutto</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Pradella</surname>
<given-names>P</given-names>
</name>
, <name name-style="western"><surname>Vaccher</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>Spina</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Tirelli</surname>
<given-names>U</given-names>
</name>
</person-group>
<year>1994</year>
<article-title>Clinical significance of positive direct antiglobulin test in patients with HIV infection</article-title>
. <source>Infection</source>
<volume>22</volume>
:<fpage>92</fpage>
–<lpage>95</lpage>
. doi:<pub-id pub-id-type="doi">10.1007/bf01739012</pub-id>
.<pub-id pub-id-type="pmid">8070936</pub-id>
</mixed-citation>
</ref>
<ref id="B16"><label>16.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lai</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Visconti</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>D'Onofrio</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Tamburrini</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>Cauda</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Leone</surname>
<given-names>G</given-names>
</name>
</person-group>
<year>2006</year>
<article-title>Lower hemoglobin levels in human immunodeficiency virus-infected patients with a positive direct antiglobulin test (DAT): relationship with DAT strength and clinical stages</article-title>
. <source>Transfusion</source>
<volume>46</volume>
:<fpage>1237</fpage>
–<lpage>1243</lpage>
. doi:<pub-id pub-id-type="doi">10.1111/j.1537-2995.2006.00876.x</pub-id>
.<pub-id pub-id-type="pmid">16836573</pub-id>
</mixed-citation>
</ref>
<ref id="B17"><label>17.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Silva-Gomes</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Appelberg</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Larsen</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Soares</surname>
<given-names>MP</given-names>
</name>
, <name name-style="western"><surname>Gomes</surname>
<given-names>MS</given-names>
</name>
</person-group>
<year>2013</year>
<article-title>Heme catabolism by heme oxygenase-1 confers host resistance to Mycobacterium infection</article-title>
. <source>Infect Immun</source>
<volume>81</volume>
:<fpage>2536</fpage>
–<lpage>2545</lpage>
. doi:<pub-id pub-id-type="doi">10.1128/IAI.00251-13</pub-id>
.<pub-id pub-id-type="pmid">23630967</pub-id>
</mixed-citation>
</ref>
<ref id="B18"><label>18.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Wagener</surname>
<given-names>BM</given-names>
</name>
, <name name-style="western"><surname>Hu</surname>
<given-names>PJ</given-names>
</name>
, <name name-style="western"><surname>Oh</surname>
<given-names>JY</given-names>
</name>
, <name name-style="western"><surname>Evans</surname>
<given-names>CA</given-names>
</name>
, <name name-style="western"><surname>Richter</surname>
<given-names>JR</given-names>
</name>
, <name name-style="western"><surname>Honavar</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Brandon</surname>
<given-names>AP</given-names>
</name>
, <name name-style="western"><surname>Creighton</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Stephens</surname>
<given-names>SW</given-names>
</name>
, <name name-style="western"><surname>Morgan</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Dull</surname>
<given-names>RO</given-names>
</name>
, <name name-style="western"><surname>Marques</surname>
<given-names>MB</given-names>
</name>
, <name name-style="western"><surname>Kerby</surname>
<given-names>JD</given-names>
</name>
, <name name-style="western"><surname>Pittet</surname>
<given-names>JF</given-names>
</name>
, <name name-style="western"><surname>Patel</surname>
<given-names>RP</given-names>
</name>
</person-group>
<year>2018</year>
<article-title>Role of heme in lung bacterial infection after trauma hemorrhage and stored red blood cell transfusion: a preclinical experimental study</article-title>
. <source>PLoS Med</source>
<volume>15</volume>
:<elocation-id>e1002522</elocation-id>
. doi:<pub-id pub-id-type="doi">10.1371/journal.pmed.1002522</pub-id>
.<pub-id pub-id-type="pmid">29522519</pub-id>
</mixed-citation>
</ref>
<ref id="B19"><label>19.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Meulenbroek</surname>
<given-names>EM</given-names>
</name>
, <name name-style="western"><surname>Wouters</surname>
<given-names>D</given-names>
</name>
, <name name-style="western"><surname>Zeerleder</surname>
<given-names>SS</given-names>
</name>
</person-group>
<year>2015</year>
<article-title>Lyse or not to lyse: clinical significance of red blood cell autoantibodies</article-title>
. <source>Blood Rev</source>
<volume>29</volume>
:<fpage>369</fpage>
–<lpage>376</lpage>
. doi:<pub-id pub-id-type="doi">10.1016/j.blre.2015.05.001</pub-id>
.<pub-id pub-id-type="pmid">26006097</pub-id>
</mixed-citation>
</ref>
<ref id="B20"><label>20.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Parker</surname>
<given-names>V</given-names>
</name>
, <name name-style="western"><surname>Tormey</surname>
<given-names>CA</given-names>
</name>
</person-group>
<year>2017</year>
<article-title>The direct antiglobulin test: indications, interpretation, and pitfalls</article-title>
. <source>Arch Pathol Lab Med</source>
<volume>141</volume>
:<fpage>305</fpage>
–<lpage>310</lpage>
. doi:<pub-id pub-id-type="doi">10.5858/arpa.2015-0444-RS</pub-id>
.<pub-id pub-id-type="pmid">28134589</pub-id>
</mixed-citation>
</ref>
<ref id="B21"><label>21.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kerkhoff</surname>
<given-names>AD</given-names>
</name>
, <name name-style="western"><surname>Wood</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Vogt</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Lawn</surname>
<given-names>SD</given-names>
</name>
</person-group>
<year>2014</year>
<article-title>Predictive value of anemia for tuberculosis in HIV-infected patients in sub-Saharan Africa: an indication for routine microbiological investigation using new rapid assays</article-title>
. <source>J Acquir Immune Defic Syndr</source>
<volume>66</volume>
:<fpage>33</fpage>
–<lpage>40</lpage>
. doi:<pub-id pub-id-type="doi">10.1097/QAI.0000000000000091</pub-id>
.<pub-id pub-id-type="pmid">24346639</pub-id>
</mixed-citation>
</ref>
<ref id="B22"><label>22.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lai</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>d'Onofrio</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Visconti</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>Tamburrini</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>Cauda</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Leone</surname>
<given-names>G</given-names>
</name>
</person-group>
<year>2006</year>
<article-title>Aetiological factors related to a positive direct antiglobulin test result in human immunodeficiency virus-infected patients</article-title>
. <source>Vox Sang</source>
<volume>90</volume>
:<fpage>325</fpage>
–<lpage>330</lpage>
. doi:<pub-id pub-id-type="doi">10.1111/j.1423-0410.2006.00755.x</pub-id>
.<pub-id pub-id-type="pmid">16635076</pub-id>
</mixed-citation>
</ref>
<ref id="B23"><label>23.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Theurl</surname>
<given-names>I</given-names>
</name>
, <name name-style="western"><surname>Hilgendorf</surname>
<given-names>I</given-names>
</name>
, <name name-style="western"><surname>Nairz</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Tymoszuk</surname>
<given-names>P</given-names>
</name>
, <name name-style="western"><surname>Haschka</surname>
<given-names>D</given-names>
</name>
, <name name-style="western"><surname>Asshoff</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>He</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Gerhardt</surname>
<given-names>LM</given-names>
</name>
, <name name-style="western"><surname>Holderried</surname>
<given-names>TA</given-names>
</name>
, <name name-style="western"><surname>Seifert</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Sopper</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Fenn</surname>
<given-names>AM</given-names>
</name>
, <name name-style="western"><surname>Anzai</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Rattik</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>McAlpine</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Theurl</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Wieghofer</surname>
<given-names>P</given-names>
</name>
, <name name-style="western"><surname>Iwamoto</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Weber</surname>
<given-names>GF</given-names>
</name>
, <name name-style="western"><surname>Harder</surname>
<given-names>NK</given-names>
</name>
, <name name-style="western"><surname>Chousterman</surname>
<given-names>BG</given-names>
</name>
, <name name-style="western"><surname>Arvedson</surname>
<given-names>TL</given-names>
</name>
, <name name-style="western"><surname>McKee</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Wang</surname>
<given-names>F</given-names>
</name>
, <name name-style="western"><surname>Lutz</surname>
<given-names>OM</given-names>
</name>
, <name name-style="western"><surname>Rezoagli</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>Babitt</surname>
<given-names>JL</given-names>
</name>
, <name name-style="western"><surname>Berra</surname>
<given-names>L</given-names>
</name>
, <name name-style="western"><surname>Prinz</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Nahrendorf</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Weiss</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Weissleder</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Lin</surname>
<given-names>HY</given-names>
</name>
, <name name-style="western"><surname>Swirski</surname>
<given-names>FK</given-names>
</name>
</person-group>
<year>2016</year>
<article-title>On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver</article-title>
. <source>Nat Med</source>
<volume>22</volume>
:<fpage>945</fpage>
–<lpage>951</lpage>
. doi:<pub-id pub-id-type="doi">10.1038/nm.4146</pub-id>
.<pub-id pub-id-type="pmid">27428900</pub-id>
</mixed-citation>
</ref>
<ref id="B24"><label>24.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Santarino</surname>
<given-names>IB</given-names>
</name>
, <name name-style="western"><surname>Viegas</surname>
<given-names>MS</given-names>
</name>
, <name name-style="western"><surname>Domingues</surname>
<given-names>NS</given-names>
</name>
, <name name-style="western"><surname>Ribeiro</surname>
<given-names>AM</given-names>
</name>
, <name name-style="western"><surname>Soares</surname>
<given-names>MP</given-names>
</name>
, <name name-style="western"><surname>Vieira</surname>
<given-names>OV</given-names>
</name>
</person-group>
<year>2017</year>
<article-title>Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis</article-title>
. <source>Sci Rep</source>
<volume>7</volume>
:<fpage>5812</fpage>
. doi:<pub-id pub-id-type="doi">10.1038/s41598-017-05687-1</pub-id>
.<pub-id pub-id-type="pmid">28724916</pub-id>
</mixed-citation>
</ref>
<ref id="B25"><label>25.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yang</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Yang</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>Shen</surname>
<given-names>L</given-names>
</name>
, <name name-style="western"><surname>Modlin</surname>
<given-names>RL</given-names>
</name>
, <name name-style="western"><surname>Shen</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>ZW</given-names>
</name>
</person-group>
<year>2018</year>
<article-title>IL-12+IL-18 cosignaling in human macrophages and lung epithelial cells activates cathelicidin and autophagy, inhibiting intracellular mycobacterial growth</article-title>
. <source>J Immunol</source>
<volume>200</volume>
:<fpage>2405</fpage>
–<lpage>2417</lpage>
. doi:<pub-id pub-id-type="doi">10.4049/jimmunol.1701073</pub-id>
.<pub-id pub-id-type="pmid">29453279</pub-id>
</mixed-citation>
</ref>
<ref id="B26"><label>26.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kimura</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Noda</surname>
<given-names>T</given-names>
</name>
, <name name-style="western"><surname>Yoshimori</surname>
<given-names>T</given-names>
</name>
</person-group>
<year>2007</year>
<article-title>Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3</article-title>
. <source>Autophagy</source>
<volume>3</volume>
:<fpage>452</fpage>
–<lpage>460</lpage>
. doi:<pub-id pub-id-type="doi">10.4161/auto.4451</pub-id>
.<pub-id pub-id-type="pmid">17534139</pub-id>
</mixed-citation>
</ref>
<ref id="B27"><label>27.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Singh</surname>
<given-names>N</given-names>
</name>
, <name name-style="western"><surname>Kansal</surname>
<given-names>P</given-names>
</name>
, <name name-style="western"><surname>Ahmad</surname>
<given-names>Z</given-names>
</name>
, <name name-style="western"><surname>Baid</surname>
<given-names>N</given-names>
</name>
, <name name-style="western"><surname>Kushwaha</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Khatri</surname>
<given-names>N</given-names>
</name>
, <name name-style="western"><surname>Kumar</surname>
<given-names>A</given-names>
</name>
</person-group>
<year>2018</year>
<article-title>Antimycobacterial effect of IFNG (interferon gamma)-induced autophagy depends on HMOX1 (heme oxygenase 1)-mediated increase in intracellular calcium levels and modulation of PPP3/calcineurin-TFEB (transcription factor EB) axis</article-title>
. <source>Autophagy</source>
<volume>14</volume>
:<fpage>972</fpage>
–<lpage>991</lpage>
. doi:<pub-id pub-id-type="doi">10.1080/15548627.2018.1436936</pub-id>
.<pub-id pub-id-type="pmid">29457983</pub-id>
</mixed-citation>
</ref>
<ref id="B28"><label>28.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Castillo</surname>
<given-names>EF</given-names>
</name>
, <name name-style="western"><surname>Dekonenko</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Arko-Mensah</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Mandell</surname>
<given-names>MA</given-names>
</name>
, <name name-style="western"><surname>Dupont</surname>
<given-names>N</given-names>
</name>
, <name name-style="western"><surname>Jiang</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Delgado-Vargas</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Timmins</surname>
<given-names>GS</given-names>
</name>
, <name name-style="western"><surname>Bhattacharya</surname>
<given-names>D</given-names>
</name>
, <name name-style="western"><surname>Yang</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Hutt</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Lyons</surname>
<given-names>CR</given-names>
</name>
, <name name-style="western"><surname>Dobos</surname>
<given-names>KM</given-names>
</name>
, <name name-style="western"><surname>Deretic</surname>
<given-names>V</given-names>
</name>
</person-group>
<year>2012</year>
<article-title>Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation</article-title>
. <source>Proc Natl Acad Sci U S A</source>
<volume>109</volume>
:<fpage>E3168</fpage>
–<lpage>EE3176</lpage>
. doi:<pub-id pub-id-type="doi">10.1073/pnas.1210500109</pub-id>
.<pub-id pub-id-type="pmid">23093667</pub-id>
</mixed-citation>
</ref>
<ref id="B29"><label>29.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Martins</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Knapp</surname>
<given-names>S</given-names>
</name>
</person-group>
<year>2018</year>
<article-title>Heme and hemolysis in innate immunity: adding insult to injury</article-title>
. <source>Curr Opin Immunol</source>
<volume>50</volume>
:<fpage>14</fpage>
–<lpage>20</lpage>
. doi:<pub-id pub-id-type="doi">10.1016/j.coi.2017.10.005</pub-id>
.<pub-id pub-id-type="pmid">29107115</pub-id>
</mixed-citation>
</ref>
<ref id="B30"><label>30.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Gozzelino</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Jeney</surname>
<given-names>V</given-names>
</name>
, <name name-style="western"><surname>Soares</surname>
<given-names>MP</given-names>
</name>
</person-group>
<year>2010</year>
<article-title>Mechanisms of cell protection by heme oxygenase-1</article-title>
. <source>Annu Rev Pharmacol Toxicol</source>
<volume>50</volume>
:<fpage>323</fpage>
–<lpage>354</lpage>
. doi:<pub-id pub-id-type="doi">10.1146/annurev.pharmtox.010909.105600</pub-id>
.<pub-id pub-id-type="pmid">20055707</pub-id>
</mixed-citation>
</ref>
<ref id="B31"><label>31.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Bolisetty</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Traylor</surname>
<given-names>AM</given-names>
</name>
, <name name-style="western"><surname>Kim</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Joseph</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Ricart</surname>
<given-names>K</given-names>
</name>
, <name name-style="western"><surname>Landar</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Agarwal</surname>
<given-names>A</given-names>
</name>
</person-group>
<year>2010</year>
<article-title>Heme oxygenase-1 inhibits renal tubular macroautophagy in acute kidney injury</article-title>
. <source>J Am Soc Nephrol</source>
<volume>21</volume>
:<fpage>1702</fpage>
–<lpage>1712</lpage>
. doi:<pub-id pub-id-type="doi">10.1681/ASN.2010030238</pub-id>
.<pub-id pub-id-type="pmid">20705711</pub-id>
</mixed-citation>
</ref>
<ref id="B32"><label>32.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yang</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Wang</surname>
<given-names>HX</given-names>
</name>
, <name name-style="western"><surname>Zhang</surname>
<given-names>L</given-names>
</name>
, <name name-style="western"><surname>Huo</surname>
<given-names>W</given-names>
</name>
, <name name-style="western"><surname>Li</surname>
<given-names>XD</given-names>
</name>
, <name name-style="western"><surname>Qi</surname>
<given-names>RQ</given-names>
</name>
, <name name-style="western"><surname>Song</surname>
<given-names>XY</given-names>
</name>
, <name name-style="western"><surname>Wei</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Gao</surname>
<given-names>XH</given-names>
</name>
, <name name-style="western"><surname>Han</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Cao</surname>
<given-names>L</given-names>
</name>
</person-group>
<year>2019</year>
<article-title>Inhibition of heme oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect</article-title>
. <source>Int J Biol Sci</source>
<volume>15</volume>
:<fpage>568</fpage>
–<lpage>578</lpage>
. doi:<pub-id pub-id-type="doi">10.7150/ijbs.29759</pub-id>
.<pub-id pub-id-type="pmid">30745843</pub-id>
</mixed-citation>
</ref>
<ref id="B33"><label>33.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Keino</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Nagae</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Mimura</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Watanabe</surname>
<given-names>K</given-names>
</name>
, <name name-style="western"><surname>Kashiwamata</surname>
<given-names>S</given-names>
</name>
</person-group>
<year>1990</year>
<article-title>Dangerous effects of tin-protoporphyrin plus photoirradiation on neonatal rats</article-title>
. <source>Eur J Pediatr</source>
<volume>149</volume>
:<fpage>278</fpage>
–<lpage>279</lpage>
. doi:<pub-id pub-id-type="doi">10.1007/bf02106294</pub-id>
.<pub-id pub-id-type="pmid">2303077</pub-id>
</mixed-citation>
</ref>
<ref id="B34"><label>34.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Abdalla</surname>
<given-names>MY</given-names>
</name>
, <name name-style="western"><surname>Ahmad</surname>
<given-names>IM</given-names>
</name>
, <name name-style="western"><surname>Switzer</surname>
<given-names>B</given-names>
</name>
, <name name-style="western"><surname>Britigan</surname>
<given-names>BE</given-names>
</name>
</person-group>
<year>2015</year>
<article-title>Induction of heme oxygenase-1 contributes to survival of Mycobacterium abscessus in human macrophages-like THP-1 cells</article-title>
. <source>Redox Biol</source>
<volume>4</volume>
:<fpage>328</fpage>
–<lpage>339</lpage>
. doi:<pub-id pub-id-type="doi">10.1016/j.redox.2015.01.012</pub-id>
.<pub-id pub-id-type="pmid">25638774</pub-id>
</mixed-citation>
</ref>
<ref id="B35"><label>35.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Mitra</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Speer</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Lin</surname>
<given-names>K</given-names>
</name>
, <name name-style="western"><surname>Ehrt</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Niederweis</surname>
<given-names>M</given-names>
</name>
</person-group>
<year>2017</year>
<article-title>PPE surface proteins are required for heme utilization by Mycobacterium tuberculosis</article-title>
. <source>mBio</source>
<volume>8</volume>
:<elocation-id>e01720-16</elocation-id>
. doi:<pub-id pub-id-type="doi">10.1128/mBio.01720-16</pub-id>
.<pub-id pub-id-type="pmid">28119467</pub-id>
</mixed-citation>
</ref>
<ref id="B36"><label>36.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Mazzolini</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Herit</surname>
<given-names>F</given-names>
</name>
, <name name-style="western"><surname>Bouchet</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Benmerah</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Benichou</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Niedergang</surname>
<given-names>F</given-names>
</name>
</person-group>
<year>2010</year>
<article-title>Inhibition of phagocytosis in HIV-1-infected macrophages relies on Nef-dependent alteration of focal delivery of recycling compartments</article-title>
. <source>Blood</source>
<volume>115</volume>
:<fpage>4226</fpage>
–<lpage>4236</lpage>
. doi:<pub-id pub-id-type="doi">10.1182/blood-2009-12-259473</pub-id>
.<pub-id pub-id-type="pmid">20299515</pub-id>
</mixed-citation>
</ref>
<ref id="B37"><label>37.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kyei</surname>
<given-names>GB</given-names>
</name>
, <name name-style="western"><surname>Dinkins</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Davis</surname>
<given-names>AS</given-names>
</name>
, <name name-style="western"><surname>Roberts</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>Singh</surname>
<given-names>SB</given-names>
</name>
, <name name-style="western"><surname>Dong</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Wu</surname>
<given-names>L</given-names>
</name>
, <name name-style="western"><surname>Kominami</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>Ueno</surname>
<given-names>T</given-names>
</name>
, <name name-style="western"><surname>Yamamoto</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Federico</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Panganiban</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Vergne</surname>
<given-names>I</given-names>
</name>
, <name name-style="western"><surname>Deretic</surname>
<given-names>V</given-names>
</name>
</person-group>
<year>2009</year>
<article-title>Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages</article-title>
. <source>J Cell Biol</source>
<volume>186</volume>
:<fpage>255</fpage>
–<lpage>268</lpage>
. doi:<pub-id pub-id-type="doi">10.1083/jcb.200903070</pub-id>
.<pub-id pub-id-type="pmid">19635843</pub-id>
</mixed-citation>
</ref>
<ref id="B38"><label>38.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Vega</surname>
<given-names>LE</given-names>
</name>
, <name name-style="western"><surname>Espinoza</surname>
<given-names>LR</given-names>
</name>
</person-group>
<year>2018</year>
<article-title>HIV infection and its effects on the development of autoimmune disorders</article-title>
. <source>Pharmacol Res</source>
<volume>129</volume>
:<fpage>1</fpage>
–<lpage>9</lpage>
. doi:<pub-id pub-id-type="doi">10.1016/j.phrs.2018.01.005</pub-id>
.<pub-id pub-id-type="pmid">29331332</pub-id>
</mixed-citation>
</ref>
<ref id="B39"><label>39.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yen</surname>
<given-names>YF</given-names>
</name>
, <name name-style="western"><surname>Lan</surname>
<given-names>YC</given-names>
</name>
, <name name-style="western"><surname>Huang</surname>
<given-names>CT</given-names>
</name>
, <name name-style="western"><surname>Jen</surname>
<given-names>IA</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Lee</surname>
<given-names>CY</given-names>
</name>
, <name name-style="western"><surname>Chuang</surname>
<given-names>PH</given-names>
</name>
, <name name-style="western"><surname>Lee</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Morisky</surname>
<given-names>DE</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>YA</given-names>
</name>
</person-group>
<year>2017</year>
<article-title>Human immunodeficiency virus infection increases the risk of incident autoimmune hemolytic anemia: a population-based cohort study in Taiwan</article-title>
. <source>J Infect Dis</source>
<volume>216</volume>
:<fpage>1000</fpage>
–<lpage>1007</lpage>
. doi:<pub-id pub-id-type="doi">10.1093/infdis/jix384</pub-id>
.<pub-id pub-id-type="pmid">29149339</pub-id>
</mixed-citation>
</ref>
<ref id="B40"><label>40.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yen</surname>
<given-names>YF</given-names>
</name>
, <name name-style="western"><surname>Chuang</surname>
<given-names>PH</given-names>
</name>
, <name name-style="western"><surname>Jen</surname>
<given-names>IA</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Lan</surname>
<given-names>YC</given-names>
</name>
, <name name-style="western"><surname>Liu</surname>
<given-names>YL</given-names>
</name>
, <name name-style="western"><surname>Lee</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>YH</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>YA</given-names>
</name>
</person-group>
<year>2017</year>
<article-title>Incidence of autoimmune diseases in a nationwide HIV/AIDS patient cohort in Taiwan, 2000–2012</article-title>
. <source>Ann Rheum Dis</source>
<volume>76</volume>
:<fpage>661</fpage>
–<lpage>665</lpage>
. doi:<pub-id pub-id-type="doi">10.1136/annrheumdis-2016-209815</pub-id>
.<pub-id pub-id-type="pmid">27590658</pub-id>
</mixed-citation>
</ref>
<ref id="B41"><label>41.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Chao</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Sieminski</surname>
<given-names>PJ</given-names>
</name>
, <name name-style="western"><surname>Owens</surname>
<given-names>CP</given-names>
</name>
, <name name-style="western"><surname>Goulding</surname>
<given-names>CW</given-names>
</name>
</person-group>
<year>2019</year>
<article-title>Iron acquisition in Mycobacterium tuberculosis</article-title>
. <source>Chem Rev</source>
<volume>119</volume>
:<fpage>1193</fpage>
–<lpage>1220</lpage>
. doi:<pub-id pub-id-type="doi">10.1021/acs.chemrev.8b00285</pub-id>
.<pub-id pub-id-type="pmid">30474981</pub-id>
</mixed-citation>
</ref>
<ref id="B42"><label>42.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Skaar</surname>
<given-names>EP</given-names>
</name>
</person-group>
<year>2010</year>
<article-title>The battle for iron between bacterial pathogens and their vertebrate hosts</article-title>
. <source>PLoS Pathog</source>
<volume>6</volume>
:<elocation-id>e1000949</elocation-id>
. doi:<pub-id pub-id-type="doi">10.1371/journal.ppat.1000949</pub-id>
.<pub-id pub-id-type="pmid">20711357</pub-id>
</mixed-citation>
</ref>
<ref id="B43"><label>43.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Tenhunen</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Marver</surname>
<given-names>HS</given-names>
</name>
, <name name-style="western"><surname>Schmid</surname>
<given-names>R</given-names>
</name>
</person-group>
<year>1968</year>
<article-title>The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase</article-title>
. <source>Proc Natl Acad Sci U S A</source>
<volume>61</volume>
:<fpage>748</fpage>
–<lpage>755</lpage>
. doi:<pub-id pub-id-type="doi">10.1073/pnas.61.2.748</pub-id>
.<pub-id pub-id-type="pmid">4386763</pub-id>
</mixed-citation>
</ref>
<ref id="B44"><label>44.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Costa</surname>
<given-names>DL</given-names>
</name>
, <name name-style="western"><surname>Namasivayam</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Amaral</surname>
<given-names>EP</given-names>
</name>
, <name name-style="western"><surname>Arora</surname>
<given-names>K</given-names>
</name>
, <name name-style="western"><surname>Chao</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Mittereder</surname>
<given-names>LR</given-names>
</name>
, <name name-style="western"><surname>Maiga</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Boshoff</surname>
<given-names>HI</given-names>
</name>
, <name name-style="western"><surname>Barry</surname>
<given-names>CE</given-names>
<suffix>III</suffix>
</name>
, <name name-style="western"><surname>Goulding</surname>
<given-names>CW</given-names>
</name>
, <name name-style="western"><surname>Andrade</surname>
<given-names>BB</given-names>
</name>
, <name name-style="western"><surname>Sher</surname>
<given-names>A</given-names>
</name>
</person-group>
<year>2016</year>
<article-title>Pharmacological inhibition of host heme oxygenase-1 suppresses Mycobacterium tuberculosis infection in vivo by a mechanism dependent on T lymphocytes</article-title>
. <source>mBio</source>
<volume>7</volume>
:<elocation-id>e01675-16</elocation-id>
. doi:<pub-id pub-id-type="doi">10.1128/mBio.01675-16</pub-id>
.<pub-id pub-id-type="pmid">27795400</pub-id>
</mixed-citation>
</ref>
<ref id="B45"><label>45.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Scharn</surname>
<given-names>CR</given-names>
</name>
, <name name-style="western"><surname>Collins</surname>
<given-names>AC</given-names>
</name>
, <name name-style="western"><surname>Nair</surname>
<given-names>VR</given-names>
</name>
, <name name-style="western"><surname>Stamm</surname>
<given-names>CE</given-names>
</name>
, <name name-style="western"><surname>Marciano</surname>
<given-names>DK</given-names>
</name>
, <name name-style="western"><surname>Graviss</surname>
<given-names>EA</given-names>
</name>
, <name name-style="western"><surname>Shiloh</surname>
<given-names>MU</given-names>
</name>
</person-group>
<year>2016</year>
<article-title>Heme oxygenase-1 regulates inflammation and mycobacterial survival in human macrophages during Mycobacterium tuberculosis infection</article-title>
. <source>J Immunol</source>
<volume>196</volume>
:<fpage>4641</fpage>
–<lpage>4649</lpage>
. doi:<pub-id pub-id-type="doi">10.4049/jimmunol.1500434</pub-id>
.<pub-id pub-id-type="pmid">27183573</pub-id>
</mixed-citation>
</ref>
<ref id="B46"><label>46.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Regev</surname>
<given-names>D</given-names>
</name>
, <name name-style="western"><surname>Surolia</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Karki</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Zolak</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Montes-Worboys</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Oliva</surname>
<given-names>O</given-names>
</name>
, <name name-style="western"><surname>Guroji</surname>
<given-names>P</given-names>
</name>
, <name name-style="western"><surname>Saini</surname>
<given-names>V</given-names>
</name>
, <name name-style="western"><surname>Steyn</surname>
<given-names>AJ</given-names>
</name>
, <name name-style="western"><surname>Agarwal</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Antony</surname>
<given-names>VB</given-names>
</name>
</person-group>
<year>2012</year>
<article-title>Heme oxygenase-1 promotes granuloma development and protects against dissemination of mycobacteria</article-title>
. <source>Lab Invest</source>
<volume>92</volume>
:<fpage>1541</fpage>
–<lpage>1552</lpage>
. doi:<pub-id pub-id-type="doi">10.1038/labinvest.2012.125</pub-id>
.<pub-id pub-id-type="pmid">22964851</pub-id>
</mixed-citation>
</ref>
<ref id="B47"><label>47.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Chinta</surname>
<given-names>KC</given-names>
</name>
, <name name-style="western"><surname>Rahman</surname>
<given-names>MA</given-names>
</name>
, <name name-style="western"><surname>Saini</surname>
<given-names>V</given-names>
</name>
, <name name-style="western"><surname>Glasgow</surname>
<given-names>JN</given-names>
</name>
, <name name-style="western"><surname>Reddy</surname>
<given-names>VP</given-names>
</name>
, <name name-style="western"><surname>Lever</surname>
<given-names>JM</given-names>
</name>
, <name name-style="western"><surname>Nhamoyebonde</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Leslie</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Wells</surname>
<given-names>RM</given-names>
</name>
, <name name-style="western"><surname>Traylor</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Madansein</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Siegal</surname>
<given-names>GP</given-names>
</name>
, <name name-style="western"><surname>Antony</surname>
<given-names>VB</given-names>
</name>
, <name name-style="western"><surname>Deshane</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Wells</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Nargan</surname>
<given-names>K</given-names>
</name>
, <name name-style="western"><surname>George</surname>
<given-names>JF</given-names>
</name>
, <name name-style="western"><surname>Ramdial</surname>
<given-names>PK</given-names>
</name>
, <name name-style="western"><surname>Agarwal</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Steyn</surname>
<given-names>A</given-names>
</name>
</person-group>
<year>2018</year>
<article-title>Microanatomic distribution of myeloid heme oxygenase-1 protects against free radical-mediated immunopathology in human tuberculosis</article-title>
. <source>Cell Rep</source>
<volume>25</volume>
:<fpage>1938</fpage>
–<lpage>1952.e5</lpage>
. doi:<pub-id pub-id-type="doi">10.1016/j.celrep.2018.10.073</pub-id>
.<pub-id pub-id-type="pmid">30428359</pub-id>
</mixed-citation>
</ref>
<ref id="B48"><label>48.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Shiloh</surname>
<given-names>MU</given-names>
</name>
, <name name-style="western"><surname>Manzanillo</surname>
<given-names>P</given-names>
</name>
, <name name-style="western"><surname>Cox</surname>
<given-names>JS</given-names>
</name>
</person-group>
<year>2008</year>
<article-title>Mycobacterium tuberculosis senses host-derived carbon monoxide during macrophage infection</article-title>
. <source>Cell Host Microbe</source>
<volume>3</volume>
:<fpage>323</fpage>
–<lpage>330</lpage>
. doi:<pub-id pub-id-type="doi">10.1016/j.chom.2008.03.007</pub-id>
.<pub-id pub-id-type="pmid">18474359</pub-id>
</mixed-citation>
</ref>
<ref id="B49"><label>49.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Waltz</surname>
<given-names>P</given-names>
</name>
, <name name-style="western"><surname>Carchman</surname>
<given-names>EH</given-names>
</name>
, <name name-style="western"><surname>Young</surname>
<given-names>AC</given-names>
</name>
, <name name-style="western"><surname>Rao</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Rosengart</surname>
<given-names>MR</given-names>
</name>
, <name name-style="western"><surname>Kaczorowski</surname>
<given-names>D</given-names>
</name>
, <name name-style="western"><surname>Zuckerbraun</surname>
<given-names>BS</given-names>
</name>
</person-group>
<year>2011</year>
<article-title>Lipopolysaccaride induces autophagic signaling in macrophages via a TLR4, heme oxygenase-1 dependent pathway</article-title>
. <source>Autophagy</source>
<volume>7</volume>
:<fpage>315</fpage>
–<lpage>320</lpage>
. doi:<pub-id pub-id-type="doi">10.4161/auto.7.3.14044</pub-id>
.<pub-id pub-id-type="pmid">21307647</pub-id>
</mixed-citation>
</ref>
<ref id="B50"><label>50.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Carchman</surname>
<given-names>EH</given-names>
</name>
, <name name-style="western"><surname>Rao</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Loughran</surname>
<given-names>PA</given-names>
</name>
, <name name-style="western"><surname>Rosengart</surname>
<given-names>MR</given-names>
</name>
, <name name-style="western"><surname>Zuckerbraun</surname>
<given-names>BS</given-names>
</name>
</person-group>
<year>2011</year>
<article-title>Heme oxygenase-1-mediated autophagy protects against hepatocyte cell death and hepatic injury from infection/sepsis in mice</article-title>
. <source>Hepatology</source>
<volume>53</volume>
:<fpage>2053</fpage>
–<lpage>2062</lpage>
. doi:<pub-id pub-id-type="doi">10.1002/hep.24324</pub-id>
.<pub-id pub-id-type="pmid">21437926</pub-id>
</mixed-citation>
</ref>
<ref id="B51"><label>51.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Wang</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Zhang</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Huang</surname>
<given-names>ZH</given-names>
</name>
, <name name-style="western"><surname>Huang</surname>
<given-names>XH</given-names>
</name>
, <name name-style="western"><surname>Zheng</surname>
<given-names>WB</given-names>
</name>
, <name name-style="western"><surname>Yin</surname>
<given-names>XF</given-names>
</name>
, <name name-style="western"><surname>Li</surname>
<given-names>YL</given-names>
</name>
, <name name-style="western"><surname>Li</surname>
<given-names>B</given-names>
</name>
, <name name-style="western"><surname>He</surname>
<given-names>QY</given-names>
</name>
</person-group>
<year>2017</year>
<article-title>Isodeoxyelephantopin induces protective autophagy in lung cancer cells via Nrf2-p62-keap1 feedback loop</article-title>
. <source>Cell Death Dis</source>
<volume>8</volume>
:<elocation-id>e2876</elocation-id>
. doi:<pub-id pub-id-type="doi">10.1038/cddis.2017.265</pub-id>
.<pub-id pub-id-type="pmid">28617433</pub-id>
</mixed-citation>
</ref>
<ref id="B52"><label>52.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Cernigliaro</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>D’Anneo</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Carlisi</surname>
<given-names>D</given-names>
</name>
, <name name-style="western"><surname>Giuliano</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Marino Gammazza</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Barone</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Longhitano</surname>
<given-names>L</given-names>
</name>
, <name name-style="western"><surname>Cappello</surname>
<given-names>F</given-names>
</name>
, <name name-style="western"><surname>Emanuele</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Distefano</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Campanella</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Calvaruso</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Lauricella</surname>
<given-names>M</given-names>
</name>
</person-group>
<year>2019</year>
<article-title>Ethanol-mediated stress promotes autophagic survival and aggressiveness of colon cancer cells via activation of Nrf2/HO-1 pathway</article-title>
. <source>Cancers (Basel)</source>
<volume>11</volume>
:<fpage>505</fpage>
. doi:<pub-id pub-id-type="doi">10.3390/cancers11040505</pub-id>
.</mixed-citation>
</ref>
<ref id="B53"><label>53.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Dai</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Wen</surname>
<given-names>Z</given-names>
</name>
, <name name-style="western"><surname>Ye</surname>
<given-names>T</given-names>
</name>
, <name name-style="western"><surname>Deng</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Zhang</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Deng</surname>
<given-names>Q</given-names>
</name>
, <name name-style="western"><surname>Yang</surname>
<given-names>Q</given-names>
</name>
, <name name-style="western"><surname>Shan</surname>
<given-names>W</given-names>
</name>
, <name name-style="western"><surname>Kornfeld</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Cai</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>X</given-names>
</name>
</person-group>
<year>2018</year>
<article-title>Empirical treatment with non-anti-tuberculosis antibiotics decreased microbiological detection in cervical tuberculous lymphadenitis</article-title>
. <source>Diagn Microbiol Infect Dis</source>
<volume>92</volume>
:<fpage>245</fpage>
–<lpage>249</lpage>
. doi:<pub-id pub-id-type="doi">10.1016/j.diagmicrobio.2018.06.008</pub-id>
.<pub-id pub-id-type="pmid">30076042</pub-id>
</mixed-citation>
</ref>
<ref id="B54"><label>54.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Zhang</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Liu</surname>
<given-names>X</given-names>
</name>
, <name name-style="western"><surname>Wang</surname>
<given-names>W</given-names>
</name>
, <name name-style="western"><surname>Cai</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Li</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>Q</given-names>
</name>
, <name name-style="western"><surname>Liao</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Zhang</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Zeng</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Zhou</surname>
<given-names>B</given-names>
</name>
, <name name-style="western"><surname>Feng</surname>
<given-names>CG</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>X</given-names>
</name>
</person-group>
<year>2016</year>
<article-title>Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages</article-title>
. <source>Cell Cycle</source>
<volume>15</volume>
:<fpage>2527</fpage>
–<lpage>2538</lpage>
. doi:<pub-id pub-id-type="doi">10.1080/15384101.2016.1215386</pub-id>
.<pub-id pub-id-type="pmid">27494776</pub-id>
</mixed-citation>
</ref>
<ref id="B55"><label>55.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Chen</surname>
<given-names>X</given-names>
</name>
, <name name-style="western"><surname>Zhang</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Liao</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Graner</surname>
<given-names>MW</given-names>
</name>
, <name name-style="western"><surname>Wu</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Yang</surname>
<given-names>Q</given-names>
</name>
, <name name-style="western"><surname>Liu</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Zhou</surname>
<given-names>B</given-names>
</name>
</person-group>
<year>2010</year>
<article-title>Reduced Th17 response in patients with tuberculosis correlates with IL-6R expression on CD4+ T cells</article-title>
. <source>Am J Respir Crit Care Med</source>
<volume>181</volume>
:<fpage>734</fpage>
–<lpage>742</lpage>
. doi:<pub-id pub-id-type="doi">10.1164/rccm.200909-1463OC</pub-id>
.<pub-id pub-id-type="pmid">20019339</pub-id>
</mixed-citation>
</ref>
<ref id="B56"><label>56.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Youssef</surname>
<given-names>LA</given-names>
</name>
, <name name-style="western"><surname>Rebbaa</surname>
<given-names>A</given-names>
</name>
, <name name-style="western"><surname>Pampou</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Weisberg</surname>
<given-names>SP</given-names>
</name>
, <name name-style="western"><surname>Stockwell</surname>
<given-names>BR</given-names>
</name>
, <name name-style="western"><surname>Hod</surname>
<given-names>EA</given-names>
</name>
, <name name-style="western"><surname>Spitalnik</surname>
<given-names>SL</given-names>
</name>
</person-group>
<year>2018</year>
<article-title>Increased erythrophagocytosis induces ferroptosis in red pulp macrophages in a mouse model of transfusion</article-title>
. <source>Blood</source>
<volume>131</volume>
:<fpage>2581</fpage>
–<lpage>2593</lpage>
. doi:<pub-id pub-id-type="doi">10.1182/blood-2017-12-822619</pub-id>
.<pub-id pub-id-type="pmid">29666112</pub-id>
</mixed-citation>
</ref>
<ref id="B57"><label>57.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Roback</surname>
<given-names>JD</given-names>
</name>
, <name name-style="western"><surname>Barclay</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Moulds</surname>
<given-names>JM</given-names>
</name>
, <name name-style="western"><surname>Denomme</surname>
<given-names>GA</given-names>
</name>
</person-group>
<year>2015</year>
<article-title>A multicenter study on the performance of a fully automated, walk-away high-throughput analyzer for pretransfusion testing in the US population</article-title>
. <source>Transfusion</source>
<volume>55</volume>
:<fpage>1522</fpage>
–<lpage>1528</lpage>
. doi:<pub-id pub-id-type="doi">10.1111/trf.13053</pub-id>
.<pub-id pub-id-type="pmid">25753019</pub-id>
</mixed-citation>
</ref>
<ref id="B58"><label>58.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Mishra</surname>
<given-names>BB</given-names>
</name>
, <name name-style="western"><surname>Lovewell</surname>
<given-names>RR</given-names>
</name>
, <name name-style="western"><surname>Olive</surname>
<given-names>AJ</given-names>
</name>
, <name name-style="western"><surname>Zhang</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Wang</surname>
<given-names>W</given-names>
</name>
, <name name-style="western"><surname>Eugenin</surname>
<given-names>E</given-names>
</name>
, <name name-style="western"><surname>Smith</surname>
<given-names>CM</given-names>
</name>
, <name name-style="western"><surname>Phuah</surname>
<given-names>JY</given-names>
</name>
, <name name-style="western"><surname>Long</surname>
<given-names>JE</given-names>
</name>
, <name name-style="western"><surname>Dubuke</surname>
<given-names>ML</given-names>
</name>
, <name name-style="western"><surname>Palace</surname>
<given-names>SG</given-names>
</name>
, <name name-style="western"><surname>Goguen</surname>
<given-names>JD</given-names>
</name>
, <name name-style="western"><surname>Baker</surname>
<given-names>RE</given-names>
</name>
, <name name-style="western"><surname>Nambi</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Mishra</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Booty</surname>
<given-names>MG</given-names>
</name>
, <name name-style="western"><surname>Baer</surname>
<given-names>CE</given-names>
</name>
, <name name-style="western"><surname>Shaffer</surname>
<given-names>SA</given-names>
</name>
, <name name-style="western"><surname>Dartois</surname>
<given-names>V</given-names>
</name>
, <name name-style="western"><surname>McCormick</surname>
<given-names>BA</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>X</given-names>
</name>
, <name name-style="western"><surname>Sassetti</surname>
<given-names>CM</given-names>
</name>
</person-group>
<year>2017</year>
<article-title>Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis</article-title>
. <source>Nat Microbiol</source>
<volume>2</volume>
:<fpage>17072</fpage>
. doi:<pub-id pub-id-type="doi">10.1038/nmicrobiol.2017.72</pub-id>
.<pub-id pub-id-type="pmid">28504669</pub-id>
</mixed-citation>
</ref>
<ref id="B59"><label>59.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Cai</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Yang</surname>
<given-names>Q</given-names>
</name>
, <name name-style="western"><surname>Liao</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Wang</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Zhang</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Nambi</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Wang</surname>
<given-names>W</given-names>
</name>
, <name name-style="western"><surname>Zhang</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Wu</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Deng</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Deng</surname>
<given-names>Q</given-names>
</name>
, <name name-style="western"><surname>Liu</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Zhou</surname>
<given-names>B</given-names>
</name>
, <name name-style="western"><surname>Jin</surname>
<given-names>Q</given-names>
</name>
, <name name-style="western"><surname>Feng</surname>
<given-names>CG</given-names>
</name>
, <name name-style="western"><surname>Sassetti</surname>
<given-names>CM</given-names>
</name>
, <name name-style="western"><surname>Wang</surname>
<given-names>F</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>X</given-names>
</name>
</person-group>
<year>2016</year>
<article-title>xCT increases tuberculosis susceptibility by regulating antimicrobial function and inflammation</article-title>
. <source>Oncotarget</source>
<volume>7</volume>
:<fpage>31001</fpage>
–<lpage>31013</lpage>
. doi:<pub-id pub-id-type="doi">10.18632/oncotarget.9052</pub-id>
.<pub-id pub-id-type="pmid">27129162</pub-id>
</mixed-citation>
</ref>
<ref id="B60"><label>60.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Wang</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Dong</surname>
<given-names>Q</given-names>
</name>
, <name name-style="western"><surname>Wang</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>He</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Zhang</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Wu</surname>
<given-names>R</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>X</given-names>
</name>
, <name name-style="western"><surname>Zhou</surname>
<given-names>B</given-names>
</name>
, <name name-style="western"><surname>He</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Kung</surname>
<given-names>HF</given-names>
</name>
, <name name-style="western"><surname>Huang</surname>
<given-names>C</given-names>
</name>
, <name name-style="western"><surname>Wei</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Huang</surname>
<given-names>JD</given-names>
</name>
, <name name-style="western"><surname>Xu</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>He</surname>
<given-names>ML</given-names>
</name>
</person-group>
<year>2016</year>
<article-title>Oblongifolin M, an active compound isolated from a Chinese medical herb Garcinia oblongifolia, potently inhibits enterovirus 71 reproduction through downregulation of ERp57</article-title>
. <source>Oncotarget</source>
<volume>7</volume>
:<fpage>8797</fpage>
–<lpage>8808</lpage>
. doi:<pub-id pub-id-type="doi">10.18632/oncotarget.7122</pub-id>
.<pub-id pub-id-type="pmid">26848777</pub-id>
</mixed-citation>
</ref>
<ref id="B61"><label>61.</label>
<mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Zhang</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Zhou</surname>
<given-names>B</given-names>
</name>
, <name name-style="western"><surname>Li</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Yue</surname>
<given-names>J</given-names>
</name>
, <name name-style="western"><surname>Yang</surname>
<given-names>H</given-names>
</name>
, <name name-style="western"><surname>Wen</surname>
<given-names>Y</given-names>
</name>
, <name name-style="western"><surname>Zhan</surname>
<given-names>S</given-names>
</name>
, <name name-style="western"><surname>Wang</surname>
<given-names>W</given-names>
</name>
, <name name-style="western"><surname>Liao</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Zhang</surname>
<given-names>M</given-names>
</name>
, <name name-style="western"><surname>Zeng</surname>
<given-names>G</given-names>
</name>
, <name name-style="western"><surname>Feng</surname>
<given-names>CG</given-names>
</name>
, <name name-style="western"><surname>Sassetti</surname>
<given-names>CM</given-names>
</name>
, <name name-style="western"><surname>Chen</surname>
<given-names>X</given-names>
</name>
</person-group>
<year>2014</year>
<article-title>Allele-specific induction of IL-1beta expression by C/EBPbeta and PU.1 contributes to increased tuberculosis susceptibility</article-title>
. <source>PLoS Pathog</source>
<volume>10</volume>
:<elocation-id>e1004426</elocation-id>
. doi:<pub-id pub-id-type="doi">10.1371/journal.ppat.1004426</pub-id>
.<pub-id pub-id-type="pmid">25329476</pub-id>
</mixed-citation>
</ref>
</ref-list>
</back>
</pmc>
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   |texte=   Autoantibody-Mediated Erythrophagocytosis Increases Tuberculosis Susceptibility in HIV Patients
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Autoantibody-Mediated Erythrophagocytosis Increases Tuberculosis Susceptibility in HIV Patients

Autoantibody-Mediated Erythrophagocytosis Increases Tuberculosis Susceptibility in HIV Patients

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