Exacerbated egg‐induced immunopathology in murine Schistosoma mansoni infection is primarily mediated by IL‐17 and restrained by IFN‐γ
Open Access
- 10 June 2011
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 41 (9), 2677-2687
- https://doi.org/10.1002/eji.201041327
Abstract
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‐γ in pathology development of 7 wk‐infected, SEA/CFA‐immunized, IL‐17−/−, IFN‐γ−/−, and IL‐17/IFN‐γ−/− mice. In IL‐17−/− mice there was significant reduction of immunopathology despite increased levels of IFN‐γ, whereas in IFN‐γ−/− mice, markedly exacerbated immunopathology correlated with an increase in IL‐17. In IL‐17/IFN‐γ−/− mice, complete resistance to SEA/CFA‐induced disease exacerbation was associated with a reduction in IL‐23p19, IL‐1β, CXCL1 and iNOS, and with an increase in IL‐5, IL‐10 and Relmα. IL‐17 and IFN‐γ 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‐γ; however, in the absence of IL‐17, IFN‐γ is capable of exerting a limited, yet significant, pathogenic function.Keywords
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