Mucosal-Associated Invariant T (MAIT) Cells Are Highly Activated and Functionally Impaired in COVID-19 Patients

Viruses. 2021 Feb 3;13(2):241. doi: 10.3390/v13020241.

Abstract

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprises mild courses of disease as well as progression to severe disease, characterised by lung and other organ failure. The immune system is considered to play a crucial role for the pathogenesis of COVID-19, although especially the contribution of innate-like T cells remains poorly understood. Here, we analysed the phenotype and function of mucosal-associated invariant T (MAIT) cells, innate-like T cells with potent antimicrobial effector function, in patients with mild and severe COVID-19 by multicolour flow cytometry. Our data indicate that MAIT cells are highly activated in patients with COVID-19, irrespective of the course of disease, and express high levels of proinflammatory cytokines such as IL-17A and TNFα ex vivo. Of note, expression of the activation marker HLA-DR positively correlated with SAPS II score, a measure of disease severity. Upon MAIT cell-specific in vitro stimulation, MAIT cells however failed to upregulate expression of the cytokines IL-17A and TNFα, as well as cytolytic proteins, that is, granzyme B and perforin. Thus, our data point towards an altered cytokine expression profile alongside an impaired antibacterial and antiviral function of MAIT cells in COVID-19 and thereby contribute to the understanding of COVID-19 immunopathogenesis.

Keywords: COVID-19; SARS-CoV-2; mucosal-associated invariant T (MAIT) cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • COVID-19 / immunology*
  • COVID-19 / physiopathology
  • Cytokines / metabolism
  • Female
  • Granzymes / metabolism
  • HLA-DR Antigens
  • Humans
  • Interleukin-17 / metabolism
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation*
  • Male
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucosal-Associated Invariant T Cells / metabolism
  • Severity of Illness Index
  • T-Lymphocyte Subsets / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • HLA-DR Antigens
  • IL17A protein, human
  • Interleukin-17
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • GZMB protein, human
  • Granzymes