MAIT cells detect and efficiently lyse bacterially-infected epithelial cells.
MAIT cells detect and efficiently lyse bacterially-infected epithelial cells.
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DOI：
10.1371/journal.ppat.1003681
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Lantz O
中科院分区：
文献类型：
--
作者：
Le Bourhis L;Dusseaux M;Bohineust A;Bessoles S;Martin E;Premel V;Coré M;Sleurs D;Serriari NE;Treiner E;Hivroz C;Sansonetti P;Gougeon ML;Soudais C;Lantz O
粘液相关不变T细胞（MAIT）是检测多种细菌和酵母菌的先天性T淋巴细胞。这种识别依赖于检测由进化上保守的主要组织相容性复合体（MHC）I类分子MR 1呈递的微生物化合物。在这里，我们表明，MAIT细胞显示对MR 1过表达的非造血细胞与细菌共培养的细胞毒活性。MAIT细胞高度表达的NK受体CD 161调节细胞因子，但不调节细菌感染细胞引发的细胞毒性反应。MAIT细胞也被感染侵袭性细菌福氏志贺氏菌后表达内源性MRI水平的上皮细胞激活并杀死。与此相反，MAIT细胞不被激活的上皮细胞感染沙门氏菌肠伤寒。最后，MAIT细胞在接受作为潜在疫苗测试的志贺氏菌-1的减毒株的人类志愿者中被激活。因此，在人类中，MAIT细胞是能够检测和杀死细菌感染细胞的最丰富的T细胞亚群。人类粘膜相关不变T细胞（MAIT）检测由MHC样分子MR 1呈递的微生物衍生化合物。这些外来抗原由多种微生物产生，包括细菌和致病性细菌或酵母。MAIT细胞在出生后不久就消耗，并构成所描述的主要抗菌T细胞亚群，因此可能在感染性疾病中发挥重要作用。在这里，我们表明，MAIT细胞识别上皮细胞感染的肠道病原体福氏志贺菌在一个过程中需要内源性MR 1，而密切相关的细菌鼠伤寒沙门氏菌不是。在识别后，感染的上皮细胞被MAIT细胞有效地裂解。我们还表明，触发的CD 161，MAIT细胞高度表达的自然杀伤受体，可以调节细胞因子，但不是这些细胞的细胞毒性功能。最后，我们提供了MAIT细胞在人类实验性肠道感染过程中被激活的证据。我们的研究为MAIT细胞的抗菌功能及其与病原菌的相互作用提供了重要的见解。
Mucosal associated invariant T cells (MAIT) are innate T lymphocytes that detect a large variety of bacteria and yeasts. This recognition depends on the detection of microbial compounds presented by the evolutionarily conserved major-histocompatibility-complex (MHC) class I molecule, MR1. Here we show that MAIT cells display cytotoxic activity towards MR1 overexpressing non-hematopoietic cells cocultured with bacteria. The NK receptor, CD161, highly expressed by MAIT cells, modulated the cytokine but not the cytotoxic response triggered by bacteria infected cells. MAIT cells are also activated by and kill epithelial cells expressing endogenous levels of MRI after infection with the invasive bacteria Shigella flexneri. In contrast, MAIT cells were not activated by epithelial cells infected by Salmonella enterica Typhimurium. Finally, MAIT cells are activated in human volunteers receiving an attenuated strain of Shigella dysenteriae-1 tested as a potential vaccine. Thus, in humans, MAIT cells are the most abundant T cell subset able to detect and kill bacteria infected cells. Human Mucosa-Associated Invariant T cells (MAIT) detect microbe-derived compounds presented by the MHC-like molecule, MR1. These foreign antigens are produced by a wide variety of microbes, including commensal and pathogenic bacteria or yeasts. MAIT cells expend shortly after birth and constitute the major antibacterial T cell subset described and, hence, could play important roles in infectious diseases. Here we show that MAIT cells recognize epithelial cells infected by the intestinal pathogen Shigella flexneri in a process requiring endogenous MR1, while the closely related bacterium Salmonella Tyhpimurium is not. Upon recognition, infected epithelial cells are efficiently lysed by MAIT cells. We also show that the triggering of CD161, a natural killer receptor highly expressed by MAIT cells, can modulate the cytokine but not the cytotoxic function of these cells. Finally, we provide evidence that MAIT cells are activated during the course of an experimental enteric infection in humans. Our study provides important insight on the antibacterial function of MAIT cells and their interaction with pathogenic bacterial species.
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