Interleukin-17A-Deficient Mice Are Highly Susceptible to Toxoplasma gondii Infection Due to Excessively Induced T. gondii HSP70 and Interferon Gamma Production.

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 of HSP70, 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 of HSP70 and IFN-γ production.