Interleukin-17A-Deficient Mice Are Highly Susceptible to Toxoplasma gondii Infection Due to Excessively Induced T. gondii HSP70 and Interferon Gamma Production
Interleukin-17A-Deficient Mice Are Highly Susceptible to Toxoplasma gondii Infection Due to Excessively Induced T. gondii HSP70 and Interferon Gamma Production
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DOI：
10.1128/iai.00399-17
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发表时间：
2017-12-01
影响因子：
3.1
通讯作者：
Aosai, Fumie
中科院分区：
文献类型：
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作者：
Moroda, Masataka;Takamoto, Masaya;Aosai, Fumie
白细胞介素17a （IL-17A）参与宿主对病原体的防御和自身免疫性疾病的发病机制。先前，我们发现过量的干扰素γ (ifn - γ)通过诱导过敏反应在弓形虫致死效应的发病机制中发挥重要作用。在本报告中，我们研究了IL-17A缺乏对小鼠宿主防御口腔弓形虫感染的影响。在弓形虫感染的急性期，il - 17a缺陷C57BL/6 （B6）小鼠的死亡率高于野生型（WT）小鼠。弓形虫感染的il - 17a缺陷小鼠肠系膜淋巴结（mLNs）和回肠中的CD4(+) T细胞比WT小鼠产生更高水平的ifn - γ。此外，与WT小鼠相比，感染il - 17a缺陷小鼠的回肠、mLNs、肝脏和脾脏中弓形虫HSP70 （t.g.h HSP70）表达水平也显著升高。在感染的IL-17A缺陷小鼠中，T.g.HSP70和ifn - γ的表达水平升高可能与IL-17A缺陷有关，因为在用重组IL-17A治疗后，它们的表达水平降至WT水平。此外，il - 17a缺陷小鼠对T.g.HSP70的过敏作用高度敏感，并且通过抗T.g.HSP70治疗il - 17a缺陷小鼠在急性期的存活率提高。HSP70单克隆抗体。这些结果表明，IL-17A通过下调T.g. hsp70和ifn - γ的产生，保护宿主免受弓形虫感染的过敏反应，在宿主抗弓形虫感染的生存中起重要作用。
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-gamma) play an important role in the pathogenesis of the lethal effects of Toxoplasma gondii 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 T. gondii infection. IL-17A-deficient C57BL/6 (B6) mice exhibited higher rates of mortality than wild-type (WT) mice during the acute phase of T. gondii infection. CD4(+) T cells in the mesenteric lymph nodes (mLNs) and ileum of T. gondii-infected IL-17A-deficient mice produced higher levels of IFN-gamma than did those of WT mice. In addition, the level of T. gondii HSP70 (T.g.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 T.g.HSP70 and IFN-gamma 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 T.g.HSP70, and the survival of IL-17A-deficient mice during the acute phase was improved by treatment with an anti-T.g.HSP70 monoclonal antibody. These results suggest that IL-17A plays an important role in host survival against T. gondii infection by protecting the host from an anaphylactic reaction via the downregulation of T.g.HSP70 and IFN-gamma production.