Macrophage-Derived Human Resistin Is Induced in Multiple Helminth Infections and Promotes Inflammatory Monocytes and Increased Parasite Burden
Identifieur interne : 006F08 ( Ncbi/Checkpoint ); précédent : 006F07; suivant : 006F09Macrophage-Derived Human Resistin Is Induced in Multiple Helminth Infections and Promotes Inflammatory Monocytes and Increased Parasite Burden
Auteurs : Jessica C. Jang [États-Unis] ; Gang Chen [États-Unis] ; Spencer H. Wang [États-Unis] ; Mark A. Barnes [États-Unis] ; Josiah I. Chung [États-Unis] ; Mali Camberis [Nouvelle-Zélande] ; Graham Le Gros [Nouvelle-Zélande] ; Philip J. Cooper [Équateur, Royaume-Uni] ; Cathy Steel [États-Unis] ; Thomas B. Nutman [États-Unis] ; Mitchell A. Lazar [États-Unis] ; Meera G. Nair [États-Unis]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2015.
Abstract
Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (h
Url:
DOI: 10.1371/journal.ppat.1004579
PubMed: 25568944
PubMed Central: 4287580
Affiliations:
- Nouvelle-Zélande, Royaume-Uni, Équateur, États-Unis
- Angleterre, Californie, Grand Londres, Maryland, Pennsylvanie
- Londres
- Université de Londres
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PMC:4287580Le document en format XML
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<author><name sortKey="Nair, Meera G" sort="Nair, Meera G" uniqKey="Nair M" first="Meera G." last="Nair">Meera G. Nair</name>
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<front><div type="abstract" xml:lang="en"><p>Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (h<italic>Retn</italic>
Tg<sup>+</sup>
). Following infection with the helminth <italic>Nippostrongylus brasiliensis</italic>
(<italic>Nb</italic>
), hResistin expression was significantly upregulated in infected tissue. Compared to control h<italic>Retn</italic>
Tg<sup>−</sup>
mice, h<italic>Retn</italic>
Tg<sup>+</sup>
mice suffered from exacerbated <italic>Nb</italic>
-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated <italic>Nb</italic>
egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode <italic>Wuchereria bancrofti</italic>
, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology.</p>
</div>
</front>
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<author><name sortKey="Shestakov, A" uniqKey="Shestakov A">A Shestakov</name>
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<author><name sortKey="Stan, D" uniqKey="Stan D">D Stan</name>
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<author><name sortKey="Lo, Dd" uniqKey="Lo D">DD Lo</name>
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<li>Royaume-Uni</li>
<li>Équateur</li>
<li>États-Unis</li>
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<region><li>Angleterre</li>
<li>Californie</li>
<li>Grand Londres</li>
<li>Maryland</li>
<li>Pennsylvanie</li>
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</settlement>
<orgName><li>Université de Londres</li>
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<tree><country name="États-Unis"><region name="Californie"><name sortKey="Jang, Jessica C" sort="Jang, Jessica C" uniqKey="Jang J" first="Jessica C." last="Jang">Jessica C. Jang</name>
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<name sortKey="Chen, Gang" sort="Chen, Gang" uniqKey="Chen G" first="Gang" last="Chen">Gang Chen</name>
<name sortKey="Chung, Josiah I" sort="Chung, Josiah I" uniqKey="Chung J" first="Josiah I." last="Chung">Josiah I. Chung</name>
<name sortKey="Lazar, Mitchell A" sort="Lazar, Mitchell A" uniqKey="Lazar M" first="Mitchell A." last="Lazar">Mitchell A. Lazar</name>
<name sortKey="Nair, Meera G" sort="Nair, Meera G" uniqKey="Nair M" first="Meera G." last="Nair">Meera G. Nair</name>
<name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name>
<name sortKey="Steel, Cathy" sort="Steel, Cathy" uniqKey="Steel C" first="Cathy" last="Steel">Cathy Steel</name>
<name sortKey="Wang, Spencer H" sort="Wang, Spencer H" uniqKey="Wang S" first="Spencer H." last="Wang">Spencer H. Wang</name>
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<country name="Nouvelle-Zélande"><noRegion><name sortKey="Camberis, Mali" sort="Camberis, Mali" uniqKey="Camberis M" first="Mali" last="Camberis">Mali Camberis</name>
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<name sortKey="Le Gros, Graham" sort="Le Gros, Graham" uniqKey="Le Gros G" first="Graham" last="Le Gros">Graham Le Gros</name>
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<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Cooper, Philip J" sort="Cooper, Philip J" uniqKey="Cooper P" first="Philip J." last="Cooper">Philip J. Cooper</name>
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