Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity
Open Access
- 2 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 22 (3), 322-335
- https://doi.org/10.1038/s41590-021-00870-z
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.Keywords
Funding Information
- Agence Nationale de la Recherche (ANR-11-IDEX-0005-02, ANR-17-CE14-0002-01, ANR-19-CE14-0020, ANR-17-RHUS-009, ANR-17-RHUS-009, ANR-17-RHUS-009, ANR-17-RHUS-009, ANR-11-IDEX-0005-02)
- Fondation pour la Recherche Médicale (EQU201903007779, EQU201903007816)
- Juvenile Diabetes Research Foundation
- Fondation Francophone pour la Recherche sur le Diabète
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