Interleukin-1 Receptor but Not Toll-Like Receptor 2 Is Essential for MyD88-Dependent Th 17 Immunity to Coccidioides Infection
Interleukin-1 Receptor but Not Toll-Like Receptor 2 Is Essential for MyD88-Dependent Th 17 Immunity to Coccidioides Infection
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DOI：
10.1128/iai.01579-13
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发表时间：
2014-05-01
影响因子：
3.1
通讯作者：
Cole, Garry T.
中科院分区：
文献类型：
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作者：
Hung, Chiung-Yu;Jimenez-Alzate, Maria del Pilar;Cole, Garry T.
产生白细胞介素-17A（IL-17 A）的CD 4（+）T辅助细胞（Th 17）已被证明对于抵抗球孢子菌属物种的肺部感染是必不可少的。然而，我们刚刚开始确定所需的模式识别受体，并了解真菌感染后导致Th 17细胞激活的信号通路。我们以前曾报道过用福尔马林灭活的小球接种Card 9（-/-）小鼠不能获得对球孢子菌感染的抵抗力。在这里，我们报告说，MyD 88（-/-）和Card 9（-/-）小鼠用活的，减毒疫苗免疫也未能获得保护性免疫这种呼吸道疾病。与Card 9（-/-）小鼠一样，接种MyD 88（-/-）小鼠在球孢子菌感染后肺中Th 17和Th 1的数量显著减少。Toll样受体2（TLR 2）和IL-1受体1型（IL-1 r1）上游均与Th 17细胞分化有关。令人惊讶的是，接种TLR 2（-/-）和野生型（WT）小鼠在肺部感染球孢子菌后显示出相似的结果，而接种IL-1 r1（-/-）小鼠显示与WT小鼠相比，其感染肺部中Th 17细胞的数量显著减少。因此，IL-1 r1/MyD 88和Card 9介导的Th 17免疫的激活对于抵抗球孢子菌感染是必不可少的。我们的数据还显示，IL-1 r1（-/-）小鼠中Th 17细胞的数量减少的程度低于MyD 88（-/-）小鼠，这增加了其他TLR参与MyD 88依赖性Th 17对球孢子菌病的免疫的可能性。Th 17细胞的抗微生物作用是促进嗜中性粒细胞早期募集到感染部位。我们的数据显示，嗜中性粒细胞是这种呼吸道疾病的疫苗免疫所必需的。
Interleukin-17A (IL-17A)-producing CD4(+) T helper (Th17) cells have been shown to be essential for defense against pulmonary infection with Coccidioides species. However, we have just begun to identify the required pattern recognition receptors and understand the signal pathways that lead to Th17 cell activation after fungal infection. We previously reported thatCard9(-/-)mice vaccinated with formalin-killed spherules failed to acquire resistance to Coccidioides infection. Here, we report that both MyD88(-/-) and Card9(-/-) mice immunized with a live, attenuated vaccine also fail to acquire protective immunity to this respiratory disease. Like Card9(-/-) mice, vaccinated MyD88(-/-)mice revealed a significant reduction in numbers of both Th17 and Th1 in their lungs after Coccidioides infection. Both Toll-like receptor 2 (TLR2) and IL-1 receptor type 1 (IL-1r1) upstream of have been implicated in Th17 cell differentiation. Surprisingly, vaccinated TLR2(-/-) and wild-type (WT) mice showed similar outcomes after pulmonary infection with Coccidioides, while vaccinated IL-1r1(-/-) mice revealed a significant reduction in the number of Th17 cells in their infected lungs compared to WT mice. Thus, activation of both IL-1r1/MyD88- and Card9-mediated Th17 immunity is essential for protection against Coccidioides infection. Our data also reveal that the numbers of Th17 cells were reduced in IL-1r1(-/-) mice to a lesser extent than in MyD88(-/-) mice, raising the possibility that other TLRs are involved in MyD88-dependent Th17 immunity to coccidioidomycosis. An antimicrobial action of Th17 cells is to promote early recruitment of neutrophils to infection sites. Our data revealed that neutrophils are required for vaccine immunity to this respiratory disease.