Tim-3 signaling blockade with α-lactose induces compensatory TIGIT expression in Plasmodium berghei ANKA-infected mice
Identifieur interne : 000160 ( Pmc/Curation ); précédent : 000159; suivant : 000161Tim-3 signaling blockade with α-lactose induces compensatory TIGIT expression in Plasmodium berghei ANKA-infected mice
Auteurs : Yiwei Zhang [République populaire de Chine] ; Ning Jiang [République populaire de Chine] ; Ting Zhang [République populaire de Chine] ; Ran Chen [République populaire de Chine] ; Ying Feng [République populaire de Chine] ; Xiaoyu Sang [République populaire de Chine] ; Na Yang [République populaire de Chine] ; Qijun Chen [République populaire de Chine]Source :
- Parasites & Vectors [ 1756-3305 ] ; 2019.
Abstract
Malaria, one of the largest health burdens worldwide, is caused by
Tim-3 expression on critical lymphocyte populations and the proportion of these cells, as well as the levels of cytokines in the sera of infected mice, were detected by flow cytometry. Further,
Increased Tim-3 expression on splenic CD8+ and splenic CD4+, and circulatory CD4+ T cells was associated with a reduction in the proportion of these cells. Furthermore, the levels of interleukin (IL)-2, IL-4, IL-6, IL-22, and interferon (IFN)-γ, but not that of tumor necrosis factor alpha (TNF-α), IL-10, and IL-9, increased to their highest levels at day 4 post-infection and decreased thereafter. Blocking Tim-3 signaling
Tim-3 on lymphocytes negatively regulates cell-mediated immunity against
Url:
DOI: 10.1186/s13071-019-3788-x
PubMed: 31711531
PubMed Central: 6849286
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Veterinary Medicine,</institution><institution>Shenyang Agricultural University,</institution></institution-wrap>Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenyang</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang</wicri:regionArea></affiliation></author><author><name sortKey="Sang, Xiaoyu" sort="Sang, Xiaoyu" uniqKey="Sang X" first="Xiaoyu" last="Sang">Xiaoyu Sang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9886 8131</institution-id><institution-id institution-id-type="GRID">grid.412557.0</institution-id><institution>Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine,</institution><institution>Shenyang Agricultural University,</institution></institution-wrap>Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenyang</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Na" sort="Yang, Na" 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level="a" type="main">Tim-3 signaling blockade with α-lactose induces compensatory TIGIT expression in <italic>Plasmodium berghei</italic> ANKA-infected mice</title><author><name sortKey="Zhang, Yiwei" sort="Zhang, Yiwei" uniqKey="Zhang Y" first="Yiwei" last="Zhang">Yiwei Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9886 8131</institution-id><institution-id institution-id-type="GRID">grid.412557.0</institution-id><institution>Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine,</institution><institution>Shenyang Agricultural University,</institution></institution-wrap>Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenyang</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Ning" sort="Jiang, Ning" uniqKey="Jiang N" first="Ning" last="Jiang">Ning Jiang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9886 8131</institution-id><institution-id institution-id-type="GRID">grid.412557.0</institution-id><institution>Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine,</institution><institution>Shenyang Agricultural University,</institution></institution-wrap>Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenyang</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Ting" sort="Zhang, Ting" uniqKey="Zhang T" first="Ting" last="Zhang">Ting Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9886 8131</institution-id><institution-id institution-id-type="GRID">grid.412557.0</institution-id><institution>Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine,</institution><institution>Shenyang Agricultural University,</institution></institution-wrap>Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenyang</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Ran" sort="Chen, Ran" uniqKey="Chen R" first="Ran" last="Chen">Ran Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9886 8131</institution-id><institution-id institution-id-type="GRID">grid.412557.0</institution-id><institution>Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine,</institution><institution>Shenyang Agricultural University,</institution></institution-wrap>Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenyang</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang</wicri:regionArea></affiliation></author><author><name sortKey="Feng, Ying" sort="Feng, Ying" uniqKey="Feng Y" first="Ying" last="Feng">Ying Feng</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9886 8131</institution-id><institution-id institution-id-type="GRID">grid.412557.0</institution-id><institution>Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine,</institution><institution>Shenyang Agricultural University,</institution></institution-wrap>Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenyang</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang</wicri:regionArea></affiliation></author><author><name sortKey="Sang, Xiaoyu" sort="Sang, Xiaoyu" uniqKey="Sang X" first="Xiaoyu" last="Sang">Xiaoyu Sang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9886 8131</institution-id><institution-id institution-id-type="GRID">grid.412557.0</institution-id><institution>Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine,</institution><institution>Shenyang Agricultural University,</institution></institution-wrap>Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenyang</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Na" sort="Yang, Na" uniqKey="Yang N" first="Na" last="Yang">Na Yang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9886 8131</institution-id><institution-id institution-id-type="GRID">grid.412557.0</institution-id><institution>Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine,</institution><institution>Shenyang Agricultural University,</institution></institution-wrap>Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenyang</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Qijun" sort="Chen, Qijun" uniqKey="Chen Q" first="Qijun" last="Chen">Qijun Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9886 8131</institution-id><institution-id institution-id-type="GRID">grid.412557.0</institution-id><institution>Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine,</institution><institution>Shenyang Agricultural University,</institution></institution-wrap>Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenyang</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2">The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang</wicri:regionArea></affiliation></author></analytic><series><title level="j">Parasites & Vectors</title><idno type="eISSN">1756-3305</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p id="Par1">Malaria, one of the largest health burdens worldwide, is caused by <italic>Plasmodium</italic> spp. infection. Upon infection, the host’s immune system begins to clear the parasites. However, <italic>Plasmodium</italic> species have evolved to escape the host’s immune clearance. T-cell immunoglobulin and mucin domain 3 (Tim-3), a surface molecule on most immune cells, is often referred to as an exhaustion marker. Galectin (Gal)-9 is a Tim-3 ligand and the T helper (Th) 1 cell response is inhibited when Gal-9 binds to Tim-3. In the present study, dynamic expression of Tim-3 on key populations of lymphocytes during infection periods of <italic>Plasmodium berghei</italic> and its significance in disease resistance and pathogenesis were explored.</p></sec><sec><title>Methods</title><p id="Par2">Tim-3 expression on critical lymphocyte populations and the proportion of these cells, as well as the levels of cytokines in the sera of infected mice, were detected by flow cytometry. Further, <italic>in vitro</italic> anti-Tim-3 assay using an anti-Tim-3 antibody and <italic>in vivo</italic> Tim-3-Gal-9 signaling blockade assays using α-lactose (an antagonist of Gal-9) were conducted. An Annexin V Apoptosis Detection Kit with propidium iodide was used to detect apoptosis. In addition, proteins associated with apoptosis in lung and spleen tissues were confirmed by Western blotting assays.</p></sec><sec><title>Results</title><p id="Par3">Increased Tim-3 expression on splenic CD8<sup>+</sup> and splenic CD4<sup>+</sup>, and circulatory CD4<sup>+</sup> T cells was associated with a reduction in the proportion of these cells. Furthermore, the levels of interleukin (IL)-2, IL-4, IL-6, IL-22, and interferon (IFN)-γ, but not that of tumor necrosis factor alpha (TNF-α), IL-10, and IL-9, increased to their highest levels at day 4 post-infection and decreased thereafter. Blocking Tim-3 signaling <italic>in vitro</italic> inhibited lymphocyte apoptosis. Tim-3-Gal-9 signaling blockade <italic>in vivo</italic> did not protect the mice, but induced the expression of the immunosuppressive molecule, T cell immunoreceptor with Ig and ITIM domains (TIGIT), in <italic>Plasmodium berghei</italic> ANKA<italic>-</italic>infected mice.</p></sec><sec><title>Conclusions</title><p id="Par4">Tim-3 on lymphocytes negatively regulates cell-mediated immunity against <italic>Plasmodium</italic> infection, and blocking Tim-3-galectin 9 signaling using α-lactose did not significantly protect the mice; however, it induced the compensatory expression of TIGIT. Further investigations are required to identify whether combined blockade of Tim-3 and TIGIT signaling could achieve a better protective effect.<graphic position="anchor" xlink:href="13071_2019_3788_Figa_HTML" id="MO100"></graphic></p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Long, Ca" uniqKey="Long C">CA Long</name></author><author><name sortKey="Zavala, F" uniqKey="Zavala F">F Zavala</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gomes, Ps" uniqKey="Gomes P">PS Gomes</name></author><author><name sortKey="Bhardwaj, J" uniqKey="Bhardwaj J">J Bhardwaj</name></author><author><name sortKey="Rivera Correa, J" uniqKey="Rivera Correa J">J Rivera-Correa</name></author><author><name sortKey="Freire De Lima, Cg" uniqKey="Freire De Lima C">CG Freire-De-Lima</name></author><author><name sortKey="Morrot, A" uniqKey="Morrot A">A Morrot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Osier, Fh" uniqKey="Osier F">FH Osier</name></author><author><name sortKey="Feng, G" uniqKey="Feng G">G Feng</name></author><author><name sortKey="Boyle, Mj" uniqKey="Boyle M">MJ Boyle</name></author><author><name sortKey="Langer, C" uniqKey="Langer C">C Langer</name></author><author><name sortKey="Zhou, J" uniqKey="Zhou J">J Zhou</name></author><author><name sortKey="Richards, Js" uniqKey="Richards J">JS Richards</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boyle, Mj" uniqKey="Boyle M">MJ Boyle</name></author><author><name sortKey="Reiling, L" uniqKey="Reiling L">L Reiling</name></author><author><name sortKey="Feng, G" uniqKey="Feng G">G Feng</name></author><author><name sortKey="Langer, C" uniqKey="Langer C">C Langer</name></author><author><name sortKey="Osier, Fh" uniqKey="Osier F">FH Osier</name></author><author><name sortKey="Aspeling Jones, H" uniqKey="Aspeling Jones H">H Aspeling-Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Imai, T" uniqKey="Imai T">T Imai</name></author><author><name sortKey="Ishida, H" uniqKey="Ishida H">H Ishida</name></author><author><name sortKey="Suzue, K" uniqKey="Suzue K">K Suzue</name></author><author><name sortKey="Taniguchi, T" uniqKey="Taniguchi T">T Taniguchi</name></author><author><name sortKey="Okada, H" uniqKey="Okada H">H Okada</name></author><author><name sortKey="Shimokawa, C" uniqKey="Shimokawa C">C Shimokawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spence, Pj" uniqKey="Spence P">PJ Spence</name></author><author><name sortKey="Langhorne, J" uniqKey="Langhorne J">J Langhorne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perez Mazliah, D" uniqKey="Perez Mazliah D">D Perez-Mazliah</name></author><author><name sortKey="Ng, Dh" uniqKey="Ng D">DH Ng</name></author><author><name sortKey="Rosario, Ap" uniqKey="Rosario A">AP Rosario</name></author><author><name sortKey="Mclaughlin, S" uniqKey="Mclaughlin S">S McLaughlin</name></author><author><name sortKey="Mastelic Gavillet, B" uniqKey="Mastelic Gavillet B">B Mastelic-Gavillet</name></author><author><name sortKey="Sodenkamp, J" uniqKey="Sodenkamp J">J Sodenkamp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crompton, Pd" uniqKey="Crompton P">PD Crompton</name></author><author><name sortKey="Moebius, J" uniqKey="Moebius J">J Moebius</name></author><author><name sortKey="Portugal, S" uniqKey="Portugal S">S Portugal</name></author><author><name sortKey="Waisberg, M" uniqKey="Waisberg M">M Waisberg</name></author><author><name sortKey="Hart, G" uniqKey="Hart G">G Hart</name></author><author><name sortKey="Garver, Ls" uniqKey="Garver L">LS Garver</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Handunnetti, Sm" uniqKey="Handunnetti S">SM Handunnetti</name></author><author><name sortKey="David, Ph" uniqKey="David P">PH David</name></author><author><name sortKey="Perera, Kl" uniqKey="Perera K">KL Perera</name></author><author><name sortKey="Mendis, Kn" uniqKey="Mendis K">KN Mendis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flick, K" uniqKey="Flick K">K Flick</name></author><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dennison, Nj" uniqKey="Dennison N">NJ Dennison</name></author><author><name sortKey="Benmarzouk Hidalgo, Oj" uniqKey="Benmarzouk Hidalgo O">OJ BenMarzouk-Hidalgo</name></author><author><name sortKey="Dimopoulos, G" uniqKey="Dimopoulos G">G Dimopoulos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gogoi, D" uniqKey="Gogoi D">D Gogoi</name></author><author><name sortKey="Biswas, D" uniqKey="Biswas D">D Biswas</name></author><author><name sortKey="Borkakoty, B" uniqKey="Borkakoty B">B Borkakoty</name></author><author><name sortKey="Mahanta, J" uniqKey="Mahanta J">J Mahanta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Keir, Me" uniqKey="Keir M">ME Keir</name></author><author><name sortKey="Butte, Mj" uniqKey="Butte M">MJ Butte</name></author><author><name sortKey="Freeman, Gj" uniqKey="Freeman G">GJ Freeman</name></author><author><name sortKey="Sharpe, Ah" uniqKey="Sharpe A">AH Sharpe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chandele, A" uniqKey="Chandele A">A Chandele</name></author><author><name sortKey="Mukerjee, P" uniqKey="Mukerjee P">P Mukerjee</name></author><author><name sortKey="Das, G" uniqKey="Das G">G Das</name></author><author><name sortKey="Ahmed, R" uniqKey="Ahmed R">R Ahmed</name></author><author><name sortKey="Chauhan, Vs" uniqKey="Chauhan V">VS Chauhan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Horne Debets, Jm" uniqKey="Horne Debets J">JM Horne-Debets</name></author><author><name sortKey="Faleiro, R" uniqKey="Faleiro R">R Faleiro</name></author><author><name sortKey="Karunarathne, Ds" uniqKey="Karunarathne D">DS Karunarathne</name></author><author><name sortKey="Liu, Xq" uniqKey="Liu X">XQ Liu</name></author><author><name sortKey="Lineburg, Ke" uniqKey="Lineburg K">KE Lineburg</name></author><author><name sortKey="Poh, Cm" uniqKey="Poh C">CM Poh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacobs, T" uniqKey="Jacobs T">T Jacobs</name></author><author><name sortKey="Plate, T" uniqKey="Plate T">T Plate</name></author><author><name sortKey="Gaworski, I" uniqKey="Gaworski I">I Gaworski</name></author><author><name sortKey="Fleischer, B" uniqKey="Fleischer B">B Fleischer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Butler, Ns" uniqKey="Butler N">NS Butler</name></author><author><name sortKey="Moebius, J" uniqKey="Moebius J">J Moebius</name></author><author><name sortKey="Pewe, Ll" uniqKey="Pewe L">LL Pewe</name></author><author><name sortKey="Traore, B" uniqKey="Traore B">B Traore</name></author><author><name sortKey="Doumbo, Ok" uniqKey="Doumbo O">OK Doumbo</name></author><author><name sortKey="Tygrett, Lt" uniqKey="Tygrett L">LT Tygrett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Romero, D" uniqKey="Romero D">D Romero</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hou, N" uniqKey="Hou N">N Hou</name></author><author><name sortKey="Zou, Y" uniqKey="Zou Y">Y Zou</name></author><author><name sortKey="Piao, X" uniqKey="Piao X">X Piao</name></author><author><name sortKey="Liu, S" uniqKey="Liu S">S Liu</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Li, S" uniqKey="Li S">S Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, C" uniqKey="Zhu C">C Zhu</name></author><author><name sortKey="Anderson, Ac" uniqKey="Anderson A">AC Anderson</name></author><author><name sortKey="Schubart, A" uniqKey="Schubart A">A Schubart</name></author><author><name sortKey="Xiong, H" uniqKey="Xiong H">H Xiong</name></author><author><name sortKey="Imitola, J" uniqKey="Imitola J">J Imitola</name></author><author><name sortKey="Khoury, Sj" uniqKey="Khoury S">SJ Khoury</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Erickson, Jj" uniqKey="Erickson J">JJ Erickson</name></author><author><name sortKey="Rogers, Mc" uniqKey="Rogers M">MC Rogers</name></author><author><name sortKey="Tollefson, Sj" uniqKey="Tollefson S">SJ Tollefson</name></author><author><name sortKey="Boyd, Kl" uniqKey="Boyd K">KL Boyd</name></author><author><name sortKey="Williams, Jv" uniqKey="Williams J">JV Williams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Jiang, N" uniqKey="Jiang N">N Jiang</name></author><author><name sortKey="Zhang, T" uniqKey="Zhang T">T Zhang</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D Wang</name></author><author><name sortKey="Feng, Y" uniqKey="Feng Y">Y Feng</name></author><author><name sortKey="Sang, X" uniqKey="Sang X">X Sang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sharma, S" uniqKey="Sharma S">S Sharma</name></author><author><name sortKey="Sundararajan, A" uniqKey="Sundararajan A">A Sundararajan</name></author><author><name sortKey="Suryawanshi, A" uniqKey="Suryawanshi A">A Suryawanshi</name></author><author><name sortKey="Kumar, N" uniqKey="Kumar N">N Kumar</name></author><author><name sortKey="Veiga Parga, T" uniqKey="Veiga Parga T">T Veiga-Parga</name></author><author><name sortKey="Kuchroo, Vk" uniqKey="Kuchroo V">VK Kuchroo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matute Bello, G" uniqKey="Matute Bello G">G Matute-Bello</name></author><author><name sortKey="Downey, G" uniqKey="Downey G">G Downey</name></author><author><name sortKey="Moore, Bb" uniqKey="Moore B">BB Moore</name></author><author><name sortKey="Groshong, Sd" uniqKey="Groshong S">SD Groshong</name></author><author><name sortKey="Matthay, Ma" uniqKey="Matthay M">MA Matthay</name></author><author><name sortKey="Slutsky, As" uniqKey="Slutsky A">AS Slutsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bakshi, Cs" uniqKey="Bakshi C">CS Bakshi</name></author><author><name sortKey="Malik, M" uniqKey="Malik M">M Malik</name></author><author><name sortKey="Mahawar, M" uniqKey="Mahawar M">M Mahawar</name></author><author><name sortKey="Kirimanjeswara, Gs" uniqKey="Kirimanjeswara G">GS Kirimanjeswara</name></author><author><name sortKey="Hazlett, Kr" uniqKey="Hazlett K">KR Hazlett</name></author><author><name sortKey="Palmer, Le" uniqKey="Palmer L">LE Palmer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mao, Xg" uniqKey="Mao X">XG Mao</name></author><author><name sortKey="Xue, Xy" uniqKey="Xue X">XY Xue</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X Zhang</name></author><author><name sortKey="Yan, M" uniqKey="Yan M">M Yan</name></author><author><name sortKey="Tu, Yy" uniqKey="Tu Y">YY Tu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dunst, J" uniqKey="Dunst J">J Dunst</name></author><author><name sortKey="Kamena, F" uniqKey="Kamena F">F Kamena</name></author><author><name sortKey="Matuschewski, K" uniqKey="Matuschewski K">K Matuschewski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qin, A" uniqKey="Qin A">A Qin</name></author><author><name sortKey="Zhong, T" uniqKey="Zhong T">T Zhong</name></author><author><name sortKey="Zou, H" uniqKey="Zou H">H Zou</name></author><author><name sortKey="Wan, X" uniqKey="Wan X">X Wan</name></author><author><name sortKey="Yao, B" uniqKey="Yao B">B Yao</name></author><author><name sortKey="Zheng, X" uniqKey="Zheng X">X Zheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ayano, M" uniqKey="Ayano M">M Ayano</name></author><author><name sortKey="Tsukamoto, H" uniqKey="Tsukamoto H">H Tsukamoto</name></author><author><name sortKey="Kohno, K" uniqKey="Kohno K">K Kohno</name></author><author><name sortKey="Ueda, N" uniqKey="Ueda N">N Ueda</name></author><author><name sortKey="Tanaka, A" uniqKey="Tanaka A">A Tanaka</name></author><author><name sortKey="Mitoma, H" uniqKey="Mitoma H">H Mitoma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, X" uniqKey="Yu X">X Yu</name></author><author><name sortKey="Harden, K" uniqKey="Harden K">K Harden</name></author><author><name sortKey="Gonzalez, Lc" uniqKey="Gonzalez L">LC Gonzalez</name></author><author><name sortKey="Francesco, M" uniqKey="Francesco M">M Francesco</name></author><author><name sortKey="Chiang, E" uniqKey="Chiang E">E Chiang</name></author><author><name sortKey="Irving, B" uniqKey="Irving B">B Irving</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nakae, S" uniqKey="Nakae S">S Nakae</name></author><author><name sortKey="Iikura, M" uniqKey="Iikura M">M Iikura</name></author><author><name sortKey="Suto, H" uniqKey="Suto H">H Suto</name></author><author><name sortKey="Akiba, H" uniqKey="Akiba H">H Akiba</name></author><author><name sortKey="Umetsu, Dt" uniqKey="Umetsu D">DT Umetsu</name></author><author><name sortKey="Dekruyff, Rh" uniqKey="Dekruyff R">RH Dekruyff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khademi, M" uniqKey="Khademi M">M Khademi</name></author><author><name sortKey="Illes, Z" uniqKey="Illes Z">Z Illes</name></author><author><name sortKey="Gielen, Aw" uniqKey="Gielen A">AW Gielen</name></author><author><name sortKey="Marta, M" uniqKey="Marta M">M Marta</name></author><author><name sortKey="Takazawa, N" uniqKey="Takazawa N">N Takazawa</name></author><author><name sortKey="Baecher Allan, C" uniqKey="Baecher Allan C">C Baecher-Allan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Monney, L" uniqKey="Monney L">L Monney</name></author><author><name sortKey="Sabatos, Ca" uniqKey="Sabatos C">CA Sabatos</name></author><author><name sortKey="Gaglia, Jl" uniqKey="Gaglia J">JL Gaglia</name></author><author><name sortKey="Ryu, A" uniqKey="Ryu A">A Ryu</name></author><author><name sortKey="Waldner, H" uniqKey="Waldner H">H Waldner</name></author><author><name sortKey="Chernova, T" uniqKey="Chernova T">T Chernova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Meng, X" uniqKey="Meng X">X Meng</name></author><author><name sortKey="Liu, X" uniqKey="Liu X">X Liu</name></author><author><name sortKey="Guo, X" uniqKey="Guo X">X Guo</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S Jiang</name></author><author><name sortKey="Chen, T" uniqKey="Chen T">T Chen</name></author><author><name sortKey="Hu, Z" uniqKey="Hu Z">Z Hu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Finney, Oc" uniqKey="Finney O">OC Finney</name></author><author><name sortKey="Nwakanma, D" uniqKey="Nwakanma D">D Nwakanma</name></author><author><name sortKey="Conway, Dj" uniqKey="Conway D">DJ Conway</name></author><author><name sortKey="Walther, M" uniqKey="Walther M">M Walther</name></author><author><name sortKey="Riley, Em" uniqKey="Riley E">EM Riley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prakash, D" uniqKey="Prakash D">D Prakash</name></author><author><name sortKey="Fesel, C" uniqKey="Fesel C">C Fesel</name></author><author><name sortKey="Jain, R" uniqKey="Jain R">R Jain</name></author><author><name sortKey="Cazenave, Pa" uniqKey="Cazenave P">PA Cazenave</name></author><author><name sortKey="Mishra, Gc" uniqKey="Mishra G">GC Mishra</name></author><author><name sortKey="Pied, S" uniqKey="Pied S">S Pied</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Healer, J" uniqKey="Healer J">J Healer</name></author><author><name sortKey="Mcguinness, D" uniqKey="Mcguinness D">D McGuinness</name></author><author><name sortKey="Carter, R" uniqKey="Carter R">R Carter</name></author><author><name sortKey="Riley, E" uniqKey="Riley E">E Riley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dodoo, D" uniqKey="Dodoo D">D Dodoo</name></author><author><name sortKey="Omer, Fm" uniqKey="Omer F">FM Omer</name></author><author><name sortKey="Todd, J" uniqKey="Todd J">J Todd</name></author><author><name sortKey="Akanmori, Bd" uniqKey="Akanmori B">BD Akanmori</name></author><author><name sortKey="Koram, Ka" uniqKey="Koram K">KA Koram</name></author><author><name sortKey="Riley, Em" uniqKey="Riley E">EM Riley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kremsner, Pg" uniqKey="Kremsner P">PG Kremsner</name></author><author><name sortKey="Neifer, S" uniqKey="Neifer S">S Neifer</name></author><author><name sortKey="Chaves, Mf" uniqKey="Chaves M">MF Chaves</name></author><author><name sortKey="Rudolph, R" uniqKey="Rudolph R">R Rudolph</name></author><author><name sortKey="Bienzle, U" uniqKey="Bienzle U">U Bienzle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morgan, Da" uniqKey="Morgan D">DA Morgan</name></author><author><name sortKey="Ruscetti, Fw" uniqKey="Ruscetti F">FW Ruscetti</name></author><author><name sortKey="Gallo, R" uniqKey="Gallo R">R Gallo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carvalho, Lh" uniqKey="Carvalho L">LH Carvalho</name></author><author><name sortKey="Sano, G" uniqKey="Sano G">G Sano</name></author><author><name sortKey="Hafalla, Jc" uniqKey="Hafalla J">JC Hafalla</name></author><author><name sortKey="Morrot, A" uniqKey="Morrot A">A Morrot</name></author><author><name sortKey="Lafaille, Ma" uniqKey="Lafaille M">MA Lafaille</name></author><author><name sortKey="Zavala, F" uniqKey="Zavala F">F Zavala</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Robinson, Lj" uniqKey="Robinson L">LJ Robinson</name></author><author><name sortKey="D Mbrain, Mc" uniqKey="D Mbrain M">MC D’Ombrain</name></author><author><name sortKey="Stanisic, Di" uniqKey="Stanisic D">DI Stanisic</name></author><author><name sortKey="Taraika, J" uniqKey="Taraika J">J Taraika</name></author><author><name sortKey="Bernard, N" uniqKey="Bernard N">N Bernard</name></author><author><name sortKey="Richards, Js" uniqKey="Richards J">JS Richards</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vaillant, Aa" uniqKey="Vaillant A">AA Vaillant</name></author><author><name sortKey="Qurie, A" uniqKey="Qurie A">A Qurie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sellau, J" uniqKey="Sellau J">J Sellau</name></author><author><name sortKey="Alvarado, Cf" uniqKey="Alvarado C">CF Alvarado</name></author><author><name sortKey="Hoenow, S" uniqKey="Hoenow S">S Hoenow</name></author><author><name sortKey="Mackroth, Ms" uniqKey="Mackroth M">MS Mackroth</name></author><author><name sortKey="Kleinschmidt, D" uniqKey="Kleinschmidt D">D Kleinschmidt</name></author><author><name sortKey="Huber, S" uniqKey="Huber S">S Huber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kossodo, S" uniqKey="Kossodo S">S Kossodo</name></author><author><name sortKey="Monso, C" uniqKey="Monso C">C Monso</name></author><author><name sortKey="Juillard, P" uniqKey="Juillard P">P Juillard</name></author><author><name sortKey="Velu, T" uniqKey="Velu T">T Velu</name></author><author><name sortKey="Goldman, M" uniqKey="Goldman M">M Goldman</name></author><author><name sortKey="Grau, Ge" uniqKey="Grau G">GE Grau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Omer, Fm" uniqKey="Omer F">FM Omer</name></author><author><name sortKey="De Souza, Jb" uniqKey="De Souza J">JB de Souza</name></author><author><name sortKey="Riley, Em" uniqKey="Riley E">EM Riley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Motyckova, G" uniqKey="Motyckova G">G Motyckova</name></author><author><name sortKey="Steensma, Dp" uniqKey="Steensma D">DP Steensma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Banerjee, H" uniqKey="Banerjee H">H Banerjee</name></author><author><name sortKey="Kane, Lp" uniqKey="Kane L">LP Kane</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nakayama, M" uniqKey="Nakayama M">M Nakayama</name></author><author><name sortKey="Akiba, H" uniqKey="Akiba H">H Akiba</name></author><author><name sortKey="Takeda, K" uniqKey="Takeda K">K Takeda</name></author><author><name sortKey="Kojima, Y" uniqKey="Kojima Y">Y Kojima</name></author><author><name sortKey="Hashiguchi, M" uniqKey="Hashiguchi M">M Hashiguchi</name></author><author><name sortKey="Azuma, M" uniqKey="Azuma M">M Azuma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chiba, S" uniqKey="Chiba S">S Chiba</name></author><author><name sortKey="Baghdadi, M" uniqKey="Baghdadi M">M Baghdadi</name></author><author><name sortKey="Akiba, H" uniqKey="Akiba H">H Akiba</name></author><author><name sortKey="Yoshiyama, H" uniqKey="Yoshiyama H">H Yoshiyama</name></author><author><name sortKey="Kinoshita, I" uniqKey="Kinoshita I">I Kinoshita</name></author><author><name sortKey="Dosaka Akita, H" uniqKey="Dosaka Akita H">H Dosaka-Akita</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Yh" uniqKey="Huang Y">YH Huang</name></author><author><name sortKey="Zhu, C" uniqKey="Zhu C">C Zhu</name></author><author><name sortKey="Kondo, Y" uniqKey="Kondo Y">Y Kondo</name></author><author><name sortKey="Anderson, Ac" uniqKey="Anderson A">AC Anderson</name></author><author><name sortKey="Gandhi, A" uniqKey="Gandhi A">A Gandhi</name></author><author><name sortKey="Russell, A" uniqKey="Russell A">A Russell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Villegas Mendez, A" uniqKey="Villegas Mendez A">A Villegas-Mendez</name></author><author><name sortKey="Inkson, Ca" uniqKey="Inkson C">CA Inkson</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">Parasit Vectors</journal-id><journal-id journal-id-type="iso-abbrev">Parasit Vectors</journal-id><journal-title-group><journal-title>Parasites & Vectors</journal-title></journal-title-group><issn pub-type="epub">1756-3305</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31711531</article-id><article-id pub-id-type="pmc">6849286</article-id><article-id pub-id-type="publisher-id">3788</article-id><article-id pub-id-type="doi">10.1186/s13071-019-3788-x</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research</subject></subj-group></article-categories><title-group><article-title>Tim-3 signaling blockade with α-lactose induces compensatory TIGIT expression in <italic>Plasmodium berghei</italic> ANKA-infected mice</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Zhang</surname><given-names>Yiwei</given-names></name><address><email>zyw@syau.edu.cn</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Jiang</surname><given-names>Ning</given-names></name><address><email>jiangning1969@163.com</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Ting</given-names></name><address><email>zhangting@stu.syau.edu.cn</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Ran</given-names></name><address><email>chenran@syau.edu.cn</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Feng</surname><given-names>Ying</given-names></name><address><email>myfengying@syau.edu.cn</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Sang</surname><given-names>Xiaoyu</given-names></name><address><email>xysang2016@syau.edu.cn</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Na</given-names></name><address><email>dayangna@syau.edu.cn</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Chen</surname><given-names>Qijun</given-names></name><address><email>qijunchen759@syau.edu.cn</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9886 8131</institution-id><institution-id institution-id-type="GRID">grid.412557.0</institution-id><institution>Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine,</institution><institution>Shenyang Agricultural University,</institution></institution-wrap>Shenyang, 110866 China</aff><aff id="Aff2"><label>2</label>The Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866 China</aff></contrib-group><pub-date pub-type="epub"><day>11</day><month>11</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>11</day><month>11</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>12</volume><elocation-id>534</elocation-id><history><date date-type="received"><day>10</day><month>9</month><year>2019</year></date><date date-type="accepted"><day>4</day><month>11</month><year>2019</year></date></history><permissions><copyright-statement>© The Author(s) 2019</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold>This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</license-p></license></permissions><abstract id="Abs1"><sec><title>Background</title><p id="Par1">Malaria, one of the largest health burdens worldwide, is caused by <italic>Plasmodium</italic> spp. infection. Upon infection, the host’s immune system begins to clear the parasites. However, <italic>Plasmodium</italic> species have evolved to escape the host’s immune clearance. T-cell immunoglobulin and mucin domain 3 (Tim-3), a surface molecule on most immune cells, is often referred to as an exhaustion marker. Galectin (Gal)-9 is a Tim-3 ligand and the T helper (Th) 1 cell response is inhibited when Gal-9 binds to Tim-3. In the present study, dynamic expression of Tim-3 on key populations of lymphocytes during infection periods of <italic>Plasmodium berghei</italic> and its significance in disease resistance and pathogenesis were explored.</p></sec><sec><title>Methods</title><p id="Par2">Tim-3 expression on critical lymphocyte populations and the proportion of these cells, as well as the levels of cytokines in the sera of infected mice, were detected by flow cytometry. Further, <italic>in vitro</italic> anti-Tim-3 assay using an anti-Tim-3 antibody and <italic>in vivo</italic> Tim-3-Gal-9 signaling blockade assays using α-lactose (an antagonist of Gal-9) were conducted. An Annexin V Apoptosis Detection Kit with propidium iodide was used to detect apoptosis. In addition, proteins associated with apoptosis in lung and spleen tissues were confirmed by Western blotting assays.</p></sec><sec><title>Results</title><p id="Par3">Increased Tim-3 expression on splenic CD8<sup>+</sup> and splenic CD4<sup>+</sup>, and circulatory CD4<sup>+</sup> T cells was associated with a reduction in the proportion of these cells. Furthermore, the levels of interleukin (IL)-2, IL-4, IL-6, IL-22, and interferon (IFN)-γ, but not that of tumor necrosis factor alpha (TNF-α), IL-10, and IL-9, increased to their highest levels at day 4 post-infection and decreased thereafter. Blocking Tim-3 signaling <italic>in vitro</italic> inhibited lymphocyte apoptosis. Tim-3-Gal-9 signaling blockade <italic>in vivo</italic> did not protect the mice, but induced the expression of the immunosuppressive molecule, T cell immunoreceptor with Ig and ITIM domains (TIGIT), in <italic>Plasmodium berghei</italic> ANKA<italic>-</italic>infected mice.</p></sec><sec><title>Conclusions</title><p id="Par4">Tim-3 on lymphocytes negatively regulates cell-mediated immunity against <italic>Plasmodium</italic> infection, and blocking Tim-3-galectin 9 signaling using α-lactose did not significantly protect the mice; however, it induced the compensatory expression of TIGIT. Further investigations are required to identify whether combined blockade of Tim-3 and TIGIT signaling could achieve a better protective effect.<graphic position="anchor" xlink:href="13071_2019_3788_Figa_HTML" id="MO100"></graphic></p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd><italic>Plasmodium berghei</italic></kwd><kwd>Tim-3</kwd><kwd>Immune escape</kwd><kwd>Cytokine</kwd><kwd>α-lactose</kwd><kwd>TIGIT</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100001809</institution-id><institution>National Natural Science Foundation of China</institution></institution-wrap></funding-source><award-id>81420108023</award-id><award-id>81772219</award-id><principal-award-recipient><name><surname>Jiang</surname><given-names>Ning</given-names></name><name><surname>Chen</surname><given-names>Qijun</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution>CAMS Innovation Fund for Medical Sciences (CIFMS)</institution></funding-source><award-id>2019-I2M-5-042</award-id><principal-award-recipient><name><surname>Jiang</surname><given-names>Ning</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution>distinguished scientist grant from Shenyang Agricultural University</institution></funding-source><award-id>8804-880416076</award-id><principal-award-recipient><name><surname>Jiang</surname><given-names>Ning</given-names></name></principal-award-recipient></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2019</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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