| First Author | Rutitzky LI | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 9 | Pages | 2677-87 |
| PubMed ID | 21660933 | Mgi Jnum | J:176818 |
| Mgi Id | MGI:5292787 | Doi | 10.1002/eji.201041327 |
| Citation | Rutitzky LI, et al. (2011) Exacerbated egg-induced immunopathology in murine Schistosoma mansoni infection is primarily mediated by IL-17 and restrained by IFN-gamma. Eur J Immunol 41(9):2677-87 |
| abstractText | In schistosomiasis, the severity of CD4(+) T-cell-mediated hepatic granulomatous inflammation against parasite eggs varies considerably in humans and among mouse strains. In C57BL/6 mice, pronounced exacerbation of immunopathology induced by immunization with schistosome egg Ag in CFA (SEA/CFA) substantially recapitulates the natural high pathology seen in CBA mice; both are associated with a significant elevation of Th17- and Th1-cell-derived proinflammatory cytokines. We now investigated the relative contribution of the effector cytokines IL-17 and IFN-gamma in pathology development of 7 wk-infected, SEA/CFA-immunized, IL-17(-/-) , IFN-gamma(-/-) , and IL-17/IFN-gamma(-/-) mice. In IL-17(-/-) mice there was significant reduction of immunopathology despite increased levels of IFN-gamma, whereas in IFN-gamma(-/-) mice, markedly exacerbated immunopathology correlated with an increase in IL-17. In IL-17/IFN-gamma(-/-) mice, complete resistance to SEA/CFA-induced disease exacerbation was associated with a reduction in IL-23p19, IL-1beta, CXCL1 and iNOS, and with an increase in IL-5, IL-10 and Relmalpha. IL-17 and IFN-gamma were derived from distinct CD4(+) T cells in which production of each cytokine was suppressed by the other. Our results indicate that severe immunopathology in murine schistosomiasis is mainly driven by IL-17 and regulated by IFN-gamma; however, in the absence of IL-17, IFN-gamma is capable of exerting a limited, yet significant, pathogenic function. |
