Respective IL-17A production by γδ T and Th17 cells and its implication in host defense against chlamydial lung infection
Respective IL-17A production by γδ T and Th17 cells and its implication in host defense against chlamydial lung infection
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DOI：
10.1038/cmi.2016.53
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发表时间：
2017-10-01
影响因子：
24.1
通讯作者：
Yang, Xi
中科院分区：
文献类型：
--
作者：
Bai, Hong;Gao, Xiaoling;Yang, Xi
IL-17 A的作用在保护免受衣原体（一种专性细胞内细菌病原体）的肺部感染中是重要的。在这项研究中，我们探讨了衣原体肺部感染中IL-17 A的产生者，并专门测试了主要IL-17 A产生者在保护性免疫中的作用。我们发现γ δ T细胞和Th 17细胞分别是衣原体感染早期和晚期IL-17 A的主要产生者。在感染后早期（p.i.）阶段，当大多数γ δ T细胞产生IL-17 A时，不能改变Th 1应答和细菌清除。相比之下，在IL-17 A主要由Th 17产生时（感染后第7天）的IL-17 A的阻断可抑制IL-17 A的表达。显著降低Th 1应答并增加衣原体生长。数据表明，γ δ T细胞在感染的非常早期阶段是IL-17 A的最高生产者，但IL-17 A赋予的保护作用主要由Th 17细胞介导。此外，我们发现γ δ T细胞的耗竭减少了树突状细胞产生的IL-1 α，这与Th 17应答的减少有关。这一发现有助于了解IL-17 A在不同感染中的不同作用，并通过靶向IL-17 A开发针对感染性疾病的预防和治疗方法。
The role of IL-17A is important in protection against lung infection with Chlamydiae, an obligate intracellular bacterial pathogen. In this study, we explored the producers of IL-17A in chlamydial lung infection and specifically tested the role of major IL-17A producers in protective immunity. We found that gamma delta T cells and Th17 cells are the major producers of IL-17A at the early and later stages of chlamydial infection, respectively. Depletion of gamma delta T cells in vivo at the early postinfection (p.i.) stage, when most gamma delta T cells produce IL-17A, failed to alter Th1 responses and bacterial clearance. In contrast, the blockade of IL-17A at the time when IL-17A was mainly produced by Th17 (day 7 p.i.) markedly reduced the Th1 response and increased chlamydial growth. The data suggest that the gamma delta T cell is the highest producer of IL-17A in the very early stages of infection, but the protection conferred by IL-17A is mainly mediated by Th17 cells. In addition, we found that depletion of gamma delta T cells reduced IL-1 alpha production by dendritic cells, which was associated with a reduced Th17 response. This finding is helpful to understand the variable role of IL-17A in different infections and to develop preventive and therapeutic approaches against infectious diseases by targeting IL-17A.