近日，法国巴黎大学Agnès Lehuen及其课题组发现SARS-CoV-2感染的结局与MAIT细胞激活和细胞毒性有关。该项研究成果于2021年2月2日在线发表在《自然—免疫学》杂志上。

研究人员分析了208名不同疾病阶段患者队列中的免疫细胞格局，重点是粘膜相关恒定T（MAIT）细胞。血液中MAIT细胞的频率大大降低。它们表现出很强的活化和细胞毒性表型，在肺部更为明显。血液MAIT细胞改变与其他先天细胞、促炎细胞因子（尤其是白介素（IL）-18）的活化以及SARS-CoV-2感染的严重程度和死亡率成正相关。

研究人员还确定了单核细胞/巨噬细胞干扰素（IFN）-α–IL-18细胞因子转移，以及感染的巨噬细胞以MR1依赖性方式诱导MAIT细胞的细胞毒性的能力。

总之，这些结果表明，由于IFN-α-IL-18失衡导致MAIT细胞功能改变，进而影响疾病严重程度，其治疗方法可预防COVID-19加重期间的有害炎症。 

据了解，免疫系统功能异常在COVID-19的严重程度和死亡率中至关重要。MAIT细胞是先天性T细胞，参与粘膜免疫和保护免受病毒感染。

附：英文原文

Title: Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity

Author: Hlose Flament, Matthieu Rouland, Lucie Beaudoin, Amine Toubal, Lo Bertrand, Samuel Lebourgeois, Camille Rousseau, Pauline Soulard, Zouriatou Gouda, Lucie Cagninacci, Antoine C. Monteiro, Margarita Hurtado-Nedelec, Sandrine Luce, Karine Bailly, Muriel Andrieu, Benjamin Saintpierre, Franck Letourneur, Youenn Jouan, Mustapha Si-Tahar, Thomas Baranek, Christophe Paget, Christian Boitard, Anas Vallet-Pichard, Jean-Franois Gautier, Nadine Ajzenberg, Benjamin Terrier, Frdric Pne, Jade Ghosn, Xavier Lescure, Yazdan Yazdanpanah, Benoit Visseaux, Diane Descamps, Jean-Franois Timsit, Renato C. Monteiro, Agns Lehuen

Issue&Volume: 2021-02-02

Abstract: Immune system dysfunction is paramount in coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in cohorts totaling 208 patients with various stages of disease. MAIT cell frequency is strongly reduced in blood. They display a strong activated and cytotoxic phenotype that is more pronounced in lungs. Blood MAIT cell alterations positively correlate with the activation of other innate cells, proinflammatory cytokines, notably interleukin (IL)-18, and with the severity and mortality of severe acute respiratory syndrome coronavirus 2 infection. We also identified a monocyte/macrophage interferon (IFN)-α–IL-18 cytokine shift and the ability of infected macrophages to induce the cytotoxicity of MAIT cells in an MR1-dependent manner. Together, our results suggest that altered MAIT cell functions due to IFN-α–IL-18 imbalance contribute to disease severity, and their therapeutic manipulation may prevent deleterious inflammation in COVID-19 aggravation.

DOI: 10.1038/s41590-021-00870-z

Source: https://www.nature.com/articles/s41590-021-00870-z