Umemura Masayuki, Yahagi Ayano, Hamada Satoru, Begum Mst Dilara, Watanabe Hisami, Kawakami Kazuyoshi, Suda Takashi, Sudo Katsuko, Nakae Susumu, Iwakura Yoichiro, Matsuzaki Goro
Molecular Microbiology Group, Center of Molecular Biosciences, University of the Ryukyus, 1 Senbaru, Nishihara, Okinawa 903-0213, Japan.
J Immunol. 2007 Mar 15;178(6):3786-96. doi: 10.4049/jimmunol.178.6.3786.
IL-17 is a cytokine that induces neutrophil-mediated inflammation, but its role in protective immunity against intracellular bacterial infection remains unclear. In the present study, we demonstrate that IL-17 is an important cytokine not only in the early neutrophil-mediated inflammatory response, but also in T cell-mediated IFN-gamma production and granuloma formation in response to pulmonary infection by Mycobacterium bovis bacille Calmette-Guérin (BCG). IL-17 expression in the BCG-infected lung was detected from the first day after infection and the expression depended on IL-23. Our observations indicated that gammadelta T cells are a primary source of IL-17. Lung-infiltrating T cells of IL-17-deficient mice produced less IFN-gamma in comparison to those from wild-type mice 4 wk after BCG infection. Impaired granuloma formation was also observed in the infected lungs of IL-17-deficient mice, which is consistent with the decreased delayed-type hypersensitivity response of the infected mice against mycobacterial Ag. These data suggest that IL-17 is an important cytokine in the induction of optimal Th1 response and protective immunity against mycobacterial infection.
白细胞介素-17（IL-17）是一种可诱导中性粒细胞介导的炎症反应的细胞因子，但其在针对细胞内细菌感染的保护性免疫中的作用仍不清楚。在本研究中，我们证明IL-17不仅在早期中性粒细胞介导的炎症反应中是一种重要的细胞因子，而且在结核分枝杆菌卡介苗（BCG）肺部感染后的T细胞介导的γ干扰素（IFN-γ）产生和肉芽肿形成中也发挥重要作用。在感染BCG后的第一天即可检测到感染肺部的IL-17表达，且该表达依赖于白细胞介素-23（IL-23）。我们的观察结果表明，γδT细胞是IL-17的主要来源。与野生型小鼠相比，在感染BCG 4周后，IL-17缺陷小鼠的肺浸润T细胞产生的IFN-γ较少。在IL-17缺陷小鼠的感染肺部也观察到肉芽肿形成受损，这与感染小鼠对分枝杆菌抗原的迟发型超敏反应降低相一致。这些数据表明，IL-17是诱导最佳Th1反应和针对分枝杆菌感染的保护性免疫中的一种重要细胞因子。
