Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T5.
Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, Tianjin 300070, China.
Cell Mol Immunol. 2017 Oct;14(10):850-861. doi: 10.1038/cmi.2016.53. Epub 2016 Oct 31.
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 γδT cells and Th17 cells are the major producers of IL-17A at the early and later stages of chlamydial infection, respectively. Depletion of γδT cells in vivo at the early postinfection (p.i.) stage, when most γδT 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 γδ 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 γδ T cells reduced IL-1α 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.
IL-17A 的作用对于抵抗衣原体（一种专性细胞内细菌病原体）引起的肺部感染至关重要。在本研究中，我们探索了衣原体肺部感染中 IL-17A 的产生细胞，并特别测试了主要的 IL-17A 产生细胞在保护性免疫中的作用。我们发现，γδT 细胞和 Th17 细胞分别是衣原体感染早期和晚期 IL-17A 的主要产生细胞。在感染后早期（p.i.）体内耗竭 γδT 细胞，此时大多数 γδT 细胞产生 IL-17A，但并未改变 Th1 反应和清除细菌。相比之下，在 Th17 主要产生 IL-17A 的时间（第 7 天 p.i.）阻断 IL-17A 显著降低了 Th1 反应并增加了衣原体的生长。数据表明，γδT 细胞是感染早期 IL-17A 的最高产生细胞，但 IL-17A 提供的保护主要由 Th17 细胞介导。此外，我们发现耗竭 γδT 细胞可减少树突状细胞产生 IL-1α，这与 Th17 反应的减少有关。这一发现有助于理解不同感染中 IL-17A 的可变作用，并通过靶向 IL-17A 来开发针对感染性疾病的预防和治疗方法。
