Department of Microbiology and Infectious Disease, Toho University School of Medicine, Tokyo, Japan.
Infect Immun. 2012 Mar;80(3):1121-7. doi: 10.1128/IAI.05544-11. Epub 2011 Dec 5.
Interleukin-17 (IL-17) is a key factor in T helper type 17 (Th17) lineage host responses and plays critical roles in immunological control of a variety of infectious diseases. Although Legionella pneumophila, an intracellular bacterium found widely in the environment, often causes a serious and life-threatening pneumonia in humans, the contribution of IL-17 to immune function during Legionella pneumonia is unknown. In the present study, we used an experimental Legionella pneumonia infection to clarify the role of IL-17 in the resulting immune response. We observed robust production of pulmonary IL-17A and IL-17F (IL-17A/F), peaking on day 1 and declining thereafter. Upregulated production of tumor necrosis factor alpha (TNF-α), IL-6, and IL-1β, but not monocyte chemotactic protein 1 (MCP-1), was observed in Legionella-infected bone marrow-derived macrophages from BALB/c mice that had been stimulated with IL-17A or IL-17F. A significant decrease in the production of proinflammatory cytokines IL-6 and TNF-α was observed in IL-17A/F-deficient mice (BALB/c background) infected with L. pneumophila. Moreover, we found impaired neutrophil migration and lower numbers of chemokines (KC, LIX, and MIP-2) in IL-17A/F-deficient mice. IL-17A/F-deficient mice also eliminated L. pneumophila more slowly and were less likely to survive a lethal challenge. These results demonstrate that IL-17A/F plays a critical role in L. pneumophila pneumonia, probably through induction of proinflammatory cytokines and accumulation of neutrophils at the infection site.
白细胞介素-17(IL-17)是 T 辅助细胞 17(Th17)谱系宿主反应的关键因素,在多种感染性疾病的免疫控制中发挥着关键作用。虽然嗜肺军团菌是一种广泛存在于环境中的胞内细菌,但它常导致人类发生严重且危及生命的肺炎,而 IL-17 对军团菌肺炎中的免疫功能的贡献尚不清楚。在本研究中,我们使用实验性军团菌肺炎感染来阐明 IL-17 在由此产生的免疫反应中的作用。我们观察到肺部的 IL-17A 和 IL-17F(IL-17A/F)产生了强烈的反应,在第 1 天达到峰值,随后下降。用 IL-17A 或 IL-17F 刺激 BALB/c 小鼠的骨髓来源的巨噬细胞后,观察到肿瘤坏死因子-α(TNF-α)、IL-6 和 IL-1β的产生上调,但单核细胞趋化蛋白 1(MCP-1)没有上调。感染嗜肺军团菌的 IL-17A/F 缺陷型(BALB/c 背景)小鼠中促炎细胞因子 IL-6 和 TNF-α的产生显著减少。此外,我们发现 IL-17A/F 缺陷型小鼠的中性粒细胞迁移受损,趋化因子(KC、LIX 和 MIP-2)数量减少。IL-17A/F 缺陷型小鼠也更缓慢地清除嗜肺军团菌,且更不可能在致命挑战中存活。这些结果表明,IL-17A/F 在嗜肺军团菌肺炎中起着关键作用,可能通过诱导促炎细胞因子和在感染部位积累中性粒细胞来实现。