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Outcome of SARS-CoV-2 infection linked to MAIT cell activation and cytotoxicity: evidence for an IL-18 dependent mechanism

Héloïse Flament 1, 2 Matthieu Rouland 3 Lucie Beaudoin 3 Amine Toubal 3 Léo Bertrand 3 Samuel Lebourgeois 4, 5 Zouriatou Gouda 3 Camille Rousseau 3 Pauline Soulard 3 Maria Hurtado-Nedelec 2, 1 Sandrine Luce 3 Karine Bailly 3 Muriel Andrieu 3 Christian Boitard 3, 6 Anaïs Vallet-Pichard 3, 7 Jean-Francois Gautier 8 Nadine Ajzenberg 9, 10 Benjamin Terrier 11, 12 Frédéric Pene 3, 13 Jade Ghosn 4, 14 Yazdan Yazdanpanah 4, 14 Benoit Visseaux 4, 5 Diane Descamps 4, 5 Jean-Francois Timsit 4, 14 Renato Costa Monteiro 2, 1 Agnes Lehuen 3, * 
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 a cohort of 182 patients including patients at various stages of disease activity. A profound decrease of MAIT cell counts in blood of critically ill patients was observed. These cells showed a strongly activated and cytotoxic phenotype that positively correlated with circulating pro-inflammatory cytokines, notably IL-18. MAIT cell alterations markedly correlated with disease severity and patient mortality. SARS-CoV-2-infected macrophages activated MAIT cells in a cytokine-dependent manner involving an IFNα-dependent early phase and an IL-18-induced later phase. Therefore, altered MAIT cell phenotypes represent valuable biomarkers of disease severity and their therapeutic manipulation might prevent the inflammatory phase involved in COVID-19 aggravation.
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Submitted on : Wednesday, December 2, 2020 - 1:32:55 PM
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Héloïse Flament, Matthieu Rouland, Lucie Beaudoin, Amine Toubal, Léo Bertrand, et al.. Outcome of SARS-CoV-2 infection linked to MAIT cell activation and cytotoxicity: evidence for an IL-18 dependent mechanism. medRxiv : the preprint server for health sciences, [Cold Spring Harbor, NY] : Cold Spring Harbor Laboratory, [2019]-, 2020, Online ahead of print. ⟨10.1101/2020.08.31.20185082⟩. ⟨inserm-03035859⟩



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