title: Exacerbated egg-induced immunopathology in murine Schistosoma mansoni infection is primarily mediated by IL-17 and restrained by IFN-γ.
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.
authors.affiliation: Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Laura I
authors.initials: LI
authors.lastname: Rutitzky
authors.forename: Miguel J
authors.initials: MJ
authors.lastname: Stadecker
mesh_terms: D000818:Animals; D018450:Disease Progression; D004527:Egg Proteins / Q000276:immunology; D004531:Eggs; D006099:Granuloma; D007114:Immunization; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D012550:Schistosoma mansoni / Q000276:immunology* / Q000472:pathogenicity; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000503:physiopathology; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology
chemical_list: D004527:Egg Proteins; D020381:Interleukin-17; D007371:Interferon-gamma