Cutting edge:: Roles of toll-like receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection
Cutting edge:: Roles of toll-like receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection
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DOI：
10.4049/jimmunol.170.9.4432
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发表时间：
2003-05-01
影响因子：
4.4
通讯作者：
Kolls, JK
中科院分区：
文献类型：
--
作者：
Happel, KI;Zheng, MQ;Kolls, JK
IL-17的局部产生是宿主有效防御革兰氏阴性菌的重要因素。然而，通过T细胞介导IL-17加工的近端事件仍不清楚。在这项研究中，我们在体内显示，完整的Toll样受体4信号在肺是必需的诱导p19转录的IL-23和IL-17蛋白的阐述，以应对肺炎克雷伯氏菌。尽管IL-17被广泛认为是CD 4（+）T细胞产物，但我们也证明了CD 8（+）T细胞在暴露于这些细菌的树突状细胞的培养基中培养后，在体外产生了显着的IL-17。这种IL-17诱导CD 4（+）和CD 8（+）T细胞活性的主要部分是IL-23。这些数据证明了宿主对革兰氏阴性肺部感染应答中IL-17诱导的关键信号传导途径，并表明IL-23在CD 8（+）T细胞IL-17产生中的直接作用。
Local production of IL-17 is a significant factor in effective host defense against Gram-negative bacteria. However, the proximal events mediating IL-17 elaboration by Tcells remain unclear. In this study, we show in vivo that intact Toll-like receptor 4 signaling in the lung is required for induction of both the p19 transcript of IL-23 and IL-17 protein elaboration in response to Klebsiella pneumoniae. Although IL-17 is widely considered a CD4(+) T cell product, we also demonstrate significant in vitro IL-17 production by CD8(+) T cells after culture in medium from dendritic cells exposed to these bacteria. The dominant portion of this IL-17-inducing activity for both CD4(+) and CD8(+) T cells is IL-23. These data demonstrate the critical signaling pathway for IL-17 induction in the host response to Gram-negative pulmonary infection and suggest a direct role for IL-23 in CD8(+) T cell IL-17 production.