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Interleukin17A (IL-17A) is known to be involved in the host defense against pathogens and the pathogenesis of autoimmune diseases. Previously, we showed that excessive amounts of interferon gamma (IFN-γ) play an important role in the pathogenesis of the lethal effects of by inducing anaphylactic responses. In the study described in this report, we examined the effects of IL-17A deficiency on murine host defense against oral infection. IL-17A-deficient C57BL/6 (B6) mice exhibited higher rates of mortality than wild-type (WT) mice during the acute phase of infection. CD4 T cells in the mesenteric lymph nodes (mLNs) and ileum of -infected IL-17A-deficient mice produced higher levels of IFN-γ than did those of WT mice. In addition, the level of HSP70 (HSP70) expression was also significantly increased in the ileum, mLNs, liver, and spleen of infected IL-17A-deficient mice compared with that in WT mice. These elevated levels of expression of HSP70 and IFN-γ in infected IL-17A-deficient mice were presumably linked to the IL-17A defect since they decreased to WT levels after treatment with recombinant IL-17A. Furthermore, IL-17A-deficient mice were highly susceptible to the anaphylactic effect ofHSP70, and the survival of IL-17A-deficient mice during the acute phase was improved by treatment with an anti-HSP70 monoclonal antibody. These results suggest that IL-17A plays an important role in host survival against infection by protecting the host from an anaphylactic reaction via the downregulation ofHSP70 and IFN-γ production.

ABSTRACTInterleukin 1 receptor antagonist (IL-1Ra)-deficient BALB/c mice develop spontaneous arthritis resembling human rheumatoid arthritis. We herein report that infection withToxoplasma gondii, an intracellular protozoan, is capable of ameliorating the spontaneous development of arthritis in IL-1Ra-deficient mice. The onset of arthritis development was delayed and the severity score of arthritis was significantly suppressed inT. gondii-infected mice. Expression of IL-12p40 mRNA from CD11c+cells of mesenteric lymph nodes (mLN) and spleen markedly increased at 1 week after peroral infection. While CD11c+cells also produced IL-10, IL-1β, and IL-6, CD4+T cells fromT. gondii-infected mice expressed significantly high levels of T-bet and gamma interferon (IFN-γ) mRNA in both mLN and spleen. Levels of GATA-3/IL-4 mRNA or RORγt/IL-17 mRNA decreased in the infected mice, indicating Th1 cell polarization and the reduction of Th2 and Th17 cell polarization. The severity of arthritis was related to Th1 cell polarization accompanied by Th17 cell reduction, demonstrating the protective role of theT. gondii-derived Th1 response against Th17 cell-mediated arthritis in IL-1Ra-deficient mice.

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