黏膜相关固有T细胞（MAIT）对结核分枝杆菌和非结核分枝杆菌感染具有保护作用，但机制尚不明确。尽管具有固有样本性质，但MAIT细胞的反应在细菌感染中仍然存在异质性。为了全面描述对不同细菌的MAIT激活程序，我们用大肠杆菌刺激MAIT细胞，并与卡介苗比较，后者仍是唯一一种获得许可的疫苗，并且是研究人类抗分枝杆菌免疫力的可行工具。通过让激活和未激活的CD8+ MAIT细胞转录mRNA来进行测序，结果显示出每种细菌引起的MAIT细胞基因表达谱的改变，其激活标记物、转录因子、细胞因子和细胞性介质的上调表达对于MAIT细胞进行抗分枝杆菌反应至关重要。与大肠杆菌相比，卡介苗改变的MAIT细胞基因更多且能增强细胞存活和细胞性溶解作用。流式细胞仪分析同样显示，与大肠杆菌刺激相比，卡介苗刺激导致B淋巴瘤2和T-box转录因子Eomesodermin表达的蛋白质上调。因此，MAIT细胞的转录组和蛋白质表达共同显示出对卡介苗刺激产生的细胞存活和细胞性细胞毒作用的增强程度，支持卡介苗诱导MAIT细胞减轻分枝杆菌感染所产生的免疫细胞效应。版权所有©2023 Sharma，Niu，Zhang和Huang。

Mucosal-associated invariant T (MAIT) cells are protective against tuberculous and non-tuberculous mycobacterial infections with poorly understood mechanisms. Despite an innate-like nature, MAIT cell responses remain heterogeneous in bacterial infections. To comprehensively characterize MAIT activation programs responding to different bacteria, we stimulated MAIT cells with E. coli to compare with Bacillus Calmette-Guérin (BCG), which remains the only licensed vaccine and a feasible tool for investigating anti-mycobacterial immunity in humans. Upon sequencing mRNA from the activated and inactivated CD8+ MAIT cells, results demonstrated the altered MAIT cell gene profiles by each bacterium with upregulated expression of activation markers, transcription factors, cytokines, and cytolytic mediators crucial in anti-mycobacterial responses. Compared with E. coli, BCG altered more MAIT cell genes to enhance cell survival and cytolysis. Flow cytometry analyses similarly displayed a more upregulated protein expression of B-cell lymphoma 2 and T-box transcription factor Eomesodermin in BCG compared to E.coli stimulations. Thus, the transcriptomic program and protein expression of MAIT cells together displayed enhanced pro-survival and cytotoxic programs in response to BCG stimulation, supporting BCG induces cell-mediated effector responses of MAIT cells to fight mycobacterial infections.Copyright © 2023 Sharma, Niu, Zhang and Huang.