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

Héloïse Flament (1, 2, 3) , Matthieu Rouland (4, 3) , Lucie Beaudoin (4, 3) , Amine Toubal (4, 3) , Léo Bertrand (4, 3) , Samuel Lebourgeois (1, 5) , Camille Rousseau (4, 3) , Pauline Soulard (4, 3) , Zouriatou Gouda (4, 3) , Lucie Cagninacci (4, 3) , Antoine Monteiro (1, 5) , Margarita Hurtado-Nedelec (1, 2, 3) , Sandrine Luce (4, 3) , Karine Bailly (4, 3) , Muriel Andrieu (4, 3) , Benjamin Saintpierre (4, 3) , Franck Letourneur (4, 3) , Youenn Jouan (6, 7) , Mustapha Si-Tahar (6) , Thomas Baranek (6) , Christophe Paget (6) , Christian Boitard (4, 3, 8) , Anaïs Vallet-Pichard (4, 3, 8) , Jean-François Gautier (9) , Nadine Ajzenberg (1, 10) , Benjamin Terrier (8) , Frédéric Pène (4, 3, 8) , Jade Ghosn (5, 1) , Xavier Lescure (5, 1) , Yazdan Yazdanpanah (5, 1) , Benoit Visseaux (1, 5) , Diane Descamps (1, 5) , Jean-François Timsit (5, 1) , Renato Monteiro (1, 2, 3) , Agnès Lehuen (4, 3)

1 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
2 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
3 Laboratoire d'Excellence INFLAMEX [Paris]
4 IC UM3 (UMR 8104 / U1016) - Institut Cochin
5 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
6 CEPR - Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100
7 CHU Trousseau [Tours]
8 Hôpital Cochin [AP-HP]
9 Hôpital Lariboisière-Fernand-Widal [APHP]
10 LVTS (UMR_S_1148 / U1148) - Laboratoire de Recherche Vasculaire Translationnelle

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.

Domains: Life Sciences [q-bio]

Héloïse Flament, Matthieu Rouland, Lucie Beaudoin, Amine Toubal, Léo Bertrand, et al.. Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity. Nature Immunology, 2021, 22 (3), pp.322-335. ⟨10.1038/s41590-021-00870-z⟩. ⟨hal-03534664⟩