TLR adaptor MyD88 is essential for pathogen control during oral toxoplasma gondii infection but not adaptive immunity induced by a vaccine strain of the parasite.
TLR adaptor MyD88 is essential for pathogen control during oral toxoplasma gondii infection but not adaptive immunity induced by a vaccine strain of the parasite.
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DOI：
10.4049/jimmunol.181.5.3464
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发表时间：
2008-09-01
影响因子：
4.4
通讯作者：
Denkers, Eric Y.
中科院分区：
文献类型：
--
作者：
Sukhumavasi, Woraporn;Egan, Charlotte E.;Warren, Amy L.;Taylor, Gregory A.;Fox, Barbara A.;Bzik, David J.;Denkers, Eric Y.
Toll样受体（TLR）/MyD 88活化在宿主感染弓形虫过程中起重要作用。p.感染，但该信号通路在口腔感染期间的功能，其中粘膜免疫承担主要作用，还没有被检查。在这里，我们发现MyD 88 −/−小鼠未能控制寄生虫，并在口服感染后两周内死亡。在感染早期，T细胞IFN-γ的产生、中性粒细胞的募集和肠粘膜中p47 GTP酶Irgm 3/IGTP的诱导依赖于功能性MyD 88。出乎意料的是，在急性感染期间，这些反应与MyD 88无关。特别是，CD 4 + T细胞IFN-γ独立于MyD 88达到正常水平，尽管这些动物中持续缺乏IL-12。MyD 88 −/−小鼠腹腔内接种无毒力T.弓形虫尿嘧啶轴向营养体对高毒力T.弓形虫株我们的研究结果表明，MyD 88是控制弓形虫感染所必需的，但寄生虫可以触发适应性免疫，而不需要这种TLR衔接分子。
Toll-like receptor (TLR)/MyD88 activation is important in host resistance to Toxoplasma gondii during i. p. infection, but the function of this signaling pathway during oral infection, in which mucosal immunity assumes a predominant role, has not been examined. Here, we show that MyD88−/− mice fail to control the parasite and succumb within two weeks of oral infection. Early during infection, T cell IFN-γ production, recruitment of neutrophils and induction of p47 GTPase Irgm3/IGTP in the intestinal mucosa were dependent upon functional MyD88. Unexpectedly, these responses were MyD88-independent later during acute infection. In particular, CD4+ T cell IFN-γ reached normal levels independently of MyD88, despite continued absence of IL-12 in these animals. Intraperitoneal vaccination of MyD88−/− mice with an avirulent T. gondii uracil axotroph elicited robust IFN-γ responses and protective immunity to challenge with a high virulence T. gondii strain. Our results demonstrate that MyD88 is required to control Toxoplasma infection, but that the parasite can trigger adaptive immunity without the need for this TLR adaptor molecule.
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