Mucosal Associated Invariant T (MAIT) Cell Responses Differ by Sex in COVID-19 by Yu et al

Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, yet the mechanisms governing this disparity remain incompletely understood. We carried out sex-balanced sampling of peripheral blood mononuclear cells from confirmed COVID-19 inpatients and outpatients, uninfected close contacts, and healthy controls for 36-color flow cytometry and single cell RNA-sequencing. Our results revealed a pronounced reduction of circulating mucosal associated invariant T (MAIT) cells in infected females. Integration of published COVID-19 airway tissue datasets implicate that this reduction represented a major wave of MAIT cell extravasation during early infection in females. Moreover, female MAIT cells possessed an immunologically active gene signature, whereas male counterparts were pro-apoptotic. Collectively, our findings uncover a female-specific protective MAIT profile, potentially shedding light on reduced COVID-19 susceptibility in females.免疫应答的性别二态性会影响新型冠状病毒肺炎（Coronavirus Disease 2019, COVID-19）的转归，但其调控该差异的分子机制仍未完全阐明。本研究针对确诊COVID-19的住院患者、门诊患者、未感染密切接触者以及健康对照者的外周血单个核细胞（peripheral blood mononuclear cells）开展了性别均衡化采样，并进行36色流式细胞术（36-color flow cytometry）与单细胞RNA测序（single cell RNA-sequencing）检测。研究结果显示，感染新冠病毒的女性体内循环黏膜相关恒定T细胞（mucosal associated invariant T, MAIT）数量显著降低。整合已发表的COVID-19气道组织数据集后，本研究提示该细胞数量减少，对应女性在感染早期阶段MAIT细胞发生大规模渗出的过程。此外，女性MAIT细胞呈现免疫激活型基因表达特征，而男性MAIT细胞则表现出促凋亡表型。综上，本研究揭示了女性特异性的保护性MAIT细胞特征，或可为阐明女性对COVID-19易感性更低的机制提供新的研究视角。