NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8+ T cells
NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8+ T cells
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DOI：
10.1038/ni.2195
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发表时间：
2012-02-01
影响因子：
30.5
通讯作者：
Bedoui, Sammy
中科院分区：
文献类型：
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作者：
Kupz, Andreas;Guarda, Greta;Bedoui, Sammy
记忆T细胞发挥不依赖于抗原的效应器功能，但这些反应是如何调节的尚不清楚。我们发现鞭毛蛋白诱导的脾树突状细胞(DC)中NLRC4炎症小体的激活与非同源记忆CD8(+)T细胞分泌宿主保护性干扰素-γ之间存在联系，而非同源记忆CD8(+)T细胞可被鼠伤寒沙门氏菌、假结核耶尔森菌和铜绿假单胞菌所激活。我们发现CD8(α)(+)DC在通过NLRC4炎性小体感知细菌鞭毛蛋白方面特别有效。虽然这种激活会释放IL-18和IL-1β，但记忆性CD8(+)T细胞只需要IL-18来产生干扰素-γ。相反，只有IL-1β的释放，而不是IL-18的释放，依赖于Toll样受体介导的启动信号。这些发现为细菌免疫过程中非同源记忆T细胞反应的调节提供了一个全面的机制框架。
Memory T cells exert antigen-independent effector functions, but how these responses are regulated is unclear. We discovered an in vivo link between flagellin-induced NLRC4 inflammasome activation in splenic dendritic cells (DCs) and host protective interferon-gamma (IFN-gamma) secretion by noncognate memory CD8(+) T cells, which could be activated by Salmonella enterica serovar Typhimurium, Yersinia pseudotuberculosis and Pseudomonas aeruginosa. We show that CD8(alpha)(+) DCs were particularly efficient at sensing bacterial flagellin through NLRC4 inflammasomes. Although this activation released interleukin 18 (IL-18) and IL-1 beta, only IL-18 was required for IFN-gamma production by memory CD8(+) T cells. Conversely, only the release of IL-1 beta, but not IL-18, depended on priming signals mediated by Toll-like receptors. These findings provide a comprehensive mechanistic framework for the regulation of noncognate memory T cell responses during bacterial immunity.