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Department of Pathology, Tufts University School of Medicine, Boston, MA 02111
C57BL/6 mice infected with the helminth Schistosoma mansoni develop small hepatic granulomas around parasite eggs, but concomitant immunization with soluble schistosome egg Ags (SEA) in CFA (SEA/CFA) causes marked exacerbation of the lesions in a Th1-dominated environment characterized by high levels of IFN-
. We explored the cause of the severe immunopathology by using IL-12p40–/– and IL-12p35–/– mice. SEA/CFA-immunized IL-12p40–/– mice, incapable of making IL-12 or IL-23, were completely resistant to high pathology, and their SEA-stimulated lymphoid cells failed to secrete significant IFN- or IL-17. In contrast, SEA/CFA-immunized IL-12p35–/– mice, able to make IL-23 but not IL-12, developed severe lesions that correlated with high levels of IL-17, low IFN-, and an expansion of activated CD4 T cells with a CD44high/CD62Llow memory phenotype. In vivo administration of neutralizing anti-IL-17 mAb markedly inhibited hepatic granulomatous inflammation. Importantly, CBA mice, a naturally high pathology strain, also displayed elevated IL-17 levels comparable to those seen in the SEA/CFA-immunized BL/6 mice, and their lesions were similarly reduced by in vivo treatment with anti-IL-17. Our findings indicate that an IL-17-producing T cell population, likely driven by IL-23, significantly contributes to severe immunopathology in schistosomiasis.
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