Significance of mucosal associated invariant T (MAIT) Cells in SARS-CoV-2 infection

ABSTRACT

In the COVID-19 disease caused by SARS-CoV-2 virus prolonged T cell lymphopenia is common but the mechanism for it is still unknown. More importantly, the T cell lymphopenia is associated with more severe diseases. The lymphopenia in COVID-19 is more pronounced in a specialized innate-like T cell population called Mucosal Associated Invariant T cells (MAITs). MAITs are the only T cell population that expresses ACE2 receptor that SARS-CoV-2 uses for cell entry. This project aims to decipher the pathogenetic process leading to MAITs depletion in COVID-19. We hypothesize that SARS-CoV-2 can directly activate MAITs which leads to MAITs overactivation and excessive tissue destruction in the lungs where MAITs comprise a large part of the tissue-resident T cells. To test these hypotheses, we challenged MAITs isolated from healthy blood donors and controls from different age groups with SARS-CoV-2 in vitro in a BSL3 laboratory. We used a combination of multi-colour flow cytometry, RT-PCR and in situ lung immunohistochemistry to evaluate the changes in MAIT cells' functions and activation. We then translated the in vitro findings to in vivo and measured similar MAIT cell activation signatures from actual real-life patient samples obtained during acute COVID-19. Our study shows that human circulation MAIT cells are activated and declined in patients with SARS-CoV-2 infection. SARS-CoV-2 infects MAIT cells in a non-direct way.