Outcome of SARS-CoV-2 infection linked to MAIT cell activation and cytotoxicity: evidence for an IL-18 dependent mechanism - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles medRxiv : the preprint server for health sciences Year : 2020

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

Matthieu Rouland
Lucie Beaudoin
  • Function : Author
Amine Toubal
Léo Bertrand
Zouriatou Gouda
  • Function : Author
Camille Rousseau
  • Function : Author
Pauline Soulard
  • Function : Author
Sandrine Luce
Karine Bailly
  • Function : Author
Muriel Andrieu
  • Function : Author
Agnes Lehuen
  • Function : Correspondent author

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.

Domains

Immunology

Dates and versions

inserm-03035859 , version 1 (02-12-2020)

Identifiers

Cite

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, 2020, Online ahead of print. ⟨10.1101/2020.08.31.20185082⟩. ⟨inserm-03035859⟩
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