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

Authors :
Flament H
Rouland M
Beaudoin L
Toubal A
Bertrand L
Lebourgeois S
Rousseau C
Soulard P
Gouda Z
Cagninacci L
Monteiro AC
Hurtado-Nedelec M
Luce S
Bailly K
Andrieu M
Saintpierre B
Letourneur F
Jouan Y
Si-Tahar M
Baranek T
Paget C
Boitard C
Vallet-Pichard A
Gautier JF
Ajzenberg N
Terrier B
Pène F
Ghosn J
Lescure X
Yazdanpanah Y
Visseaux B
Descamps D
Timsit JF
Monteiro RC
Lehuen A
Source :
Nature immunology [Nat Immunol] 2021 Mar; Vol. 22 (3), pp. 322-335. Date of Electronic Publication: 2021 Feb 02.
Publication Year :
2021

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.

Details

Language :
English
ISSN :
1529-2916
Volume :
22
Issue :
3
Database :
MEDLINE
Journal :
Nature immunology
Publication Type :
Academic Journal
Accession number :
33531712
Full Text :
https://doi.org/10.1038/s41590-021-00870-z