Interleukin-17D Promotes Pathogenicity During Infection by Suppressing CD8T Cell Activity
Interleukin-17D Promotes Pathogenicity During Infection by Suppressing CD8T Cell Activity
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DOI：
10.3389/fimmu.2019.01172
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发表时间：
2019-06-06
影响因子：
7.3
通讯作者：
Chang, Seon Hee
中科院分区：
文献类型：
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作者：
Lee, Younghee;Clinton, Jelita;Chang, Seon Hee
白细胞介素-17D（IL-17 D）属于细胞因子IL-17家族。虽然IL-17家族的成员与炎症和宿主防御有关，但IL-17 D的功能仍不清楚。在这里，我们表明IL-17 D表达的缺乏赋予了针对李斯特菌感染的保护。在甲型流感病毒感染期间，IL-17 D的缺乏也导致体重减轻较少，病原体负荷减少。在感染期间，IL-17 D的丧失导致CD 8 T细胞活性受损。IL-17 D缺陷小鼠中的CD 8 T细胞耗竭将细菌负荷恢复至与WT小鼠中发现的水平相似的水平。类似地，与WT小鼠相比，RAG缺陷背景中的IL-17 D缺陷小鼠在细菌和病毒负荷方面没有差异。IL-17 D部分通过抑制树突状细胞的功能来控制CD 8 T细胞的活性。我们发现来自非造血区室的IL-17 D在感染期间调节保护性免疫。总之，我们的数据导致IL-17 D被鉴定为细胞内细菌和病毒感染期间的关键细胞因子，其通过调节树突状细胞来抑制CD 8 T细胞的活性。
Interleukin-17D (IL-17D) belongs to the IL-17 family of cytokines. While the members of the IL-17 family have been implicated in inflammation and host defense, the function of IL-17D remains unclear. Here, we showed that the lack of IL-17D expression confers protection against Listeria infection. A deficiency in IL-17D also resulted in less weight loss with reduced pathogen burden during influenza A virus infection. During infection, the loss of IL-17D resulted in compromised CD8T cell activity. CD8T cell depletion in IL-17D-deficient mice restored the bacterial burden to a level similar to that found in WT mice. Similarly, IL-17D-deficient mice in a RAG-deficient background had no difference in bacterial and viral burden compared to WT mice. IL-17D controlled CD8T cell activity in part by suppressing the function of dendritic cells. We found that IL-17D from the non-hematopoietic compartment regulates protective immunity during infection. Together, our data led to the identification of IL-17D as a critical cytokine during intracellular bacteria and virus infection that suppresses the activity of CD8T cells by regulating dendritic cells.