C-type lectin receptors differentially induce th17 cells and vaccine immunity to the endemic mycosis of North America.
C-type lectin receptors differentially induce th17 cells and vaccine immunity to the endemic mycosis of North America.
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DOI：
10.4049/jimmunol.1302314
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发表时间：
2014-02-01
期刊：
影响因子：
--
通讯作者：
Wüthrich M
中科院分区：
文献类型：
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作者：
Wang H;LeBert V;Hung CY;Galles K;Saijo S;Lin X;Cole GT;Klein BS;Wüthrich M
对北美地方性真菌病的疫苗免疫需要Th17细胞，但驱动这些保护性反应的模式识别受体和信号通路尚未确定。我们发现，C型凝集素受体（CLRs）发挥不同的贡献，抗真菌的Th17细胞的发展和疫苗抵抗芽生菌皮炎，荚膜组织胞浆菌和球孢子菌posadasii。获得性免疫B。皮肤炎需要Dectin-2，而针对H. capsulatum和C. posadasii感染依赖于Dectin-1和Dectin-2的先天感应，而不是Mincle。在体内追踪抗原特异性T细胞证实，Card9信号传导通路不可或缺地且专门地作用于Th17细胞的分化，同时保持它们的活化、增殖、存活和迁移完整。因此，尽管Card9信号传导是必不可少的，但CLR对针对这些地方性真菌病原体的疫苗免疫性提供了独特和不同的贡献。我们的工作为驱动疫苗免疫和Th17细胞的先天免疫机制提供了新的见解。
Vaccine immunity to the endemic mycoses of North America requires Th17 cells, but the pattern recognition receptors and signaling pathways that drive these protective responses have not been defined. We show that C-type lectin receptors (CLRs) exert divergent contributions to the development of anti-fungal Th17 cells and vaccine resistance against Blastomyces dermatitidis, Histoplasma capsulatum and Coccidioides posadasii. Acquired immunity to B. dermatitidis requires Dectin-2, whereas vaccination against H. capsulatum and C. posadasii infection depends on innate sensing by Dectin-1 and Dectin-2, but not Mincle. Tracking antigen-specific T cells in vivo established that the Card9 signaling pathway acts indispensably and exclusively on differentiation of Th17 cells, while leaving intact their activation, proliferation, survival and migration. Thus, whereas Card9 signaling is essential, CLRs offer distinct and divergent contributions to vaccine immunity against these endemic fungal pathogens. Our work provides new insight into innate immune mechanisms that drive vaccine immunity and Th17 cells.