Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
Sci Immunol. 2020 Sep 28;5(51). doi: 10.1126/sciimmunol.abe1670.
Severe COVID-19 is characterized by excessive inflammation of the lower airways. The balance of protective versus pathological immune responses in COVID-19 is incompletely understood. Mucosa-associated invariant T (MAIT) cells are antimicrobial T cells that recognize bacterial metabolites, and can also function as innate-like sensors and mediators of antiviral responses. Here, we investigated the MAIT cell compartment in COVID-19 patients with moderate and severe disease, as well as in convalescence. We show profound and preferential decline in MAIT cells in the circulation of patients with active disease paired with strong activation. Furthermore, transcriptomic analyses indicated significant MAIT cell enrichment and pro-inflammatory IL-17A bias in the airways. Unsupervised analysis identified MAIT cell CD69 and CXCR3 immunotypes associated with poor clinical outcome. MAIT cell levels normalized in the convalescent phase, consistent with dynamic recruitment to the tissues and later release back into the circulation when disease is resolved. These findings indicate that MAIT cells are engaged in the immune response against SARS-CoV-2 and suggest their possible involvement in COVID-19 immunopathogenesis.
严重的 COVID-19 的特征是下呼吸道过度炎症。COVID-19 中保护性免疫反应与病理性免疫反应之间的平衡尚未完全清楚。黏膜相关不变 T（MAIT）细胞是识别细菌代谢物的抗菌 T 细胞，也可以作为先天样传感器和抗病毒反应的介质发挥作用。在这里，我们研究了中度和重度疾病以及恢复期 COVID-19 患者的 MAIT 细胞区室。我们发现，与强烈激活配对的活动性疾病患者的循环中 MAIT 细胞明显减少并呈优先减少趋势。此外，转录组分析表明，气道中 MAIT 细胞的富集和促炎的 IL-17A 偏向明显。无监督分析确定了与不良临床结局相关的 MAIT 细胞 CD69 和 CXCR3 免疫表型。在恢复期，MAIT 细胞水平恢复正常，这与疾病消退时 MAIT 细胞向组织中的动态募集以及随后释放回循环一致。这些发现表明 MAIT 细胞参与了针对 SARS-CoV-2 的免疫反应，并提示它们可能参与了 COVID-19 的免疫发病机制。
