MAIT cells involvement in severe viral pneumonia and Acute Respiratory Distress Syndrome – MAIT-VECTORS

Viral pneumonia, including SARS-CoV-2 and influenza A virus (IAV), can culminate in acute respiratory distress syndrome (ARDS), a severe form of respiratory failure with high mortality. Uncontrolled local inflammatory response and impaired tissue repair are hallmarks of ARDS. However, lack of in-depth understanding of the immunopathology lead to limited identification of potential ‘endotypes’ who may benefit from individualized targeted therapies. Mucosal Associated Invariant T (MAIT) cells represent a peculiar lineage of T cells with a wide panel of effector functions. Thus, they emerge as potential key players and appealing targets in ARDS through their potent abilities to modulate immune response at barrier sites and promote tissue repair. Recent data from we and others indicated that MAIT cells are highly activated in patients with Sars-Cov-2 and IAV ARDS, but the associated activation mechanisms and precise functions remain unknown. Our hypothesis is that promotion of tissue repair function of MAIT cells si beneficial and protective.
In this context, we aim at investigating the implication and potential harnessing of MAIT cells in severe viral pneumonias and associated ARDS by combining a dedicated clinical study and two relevant models of IAV pneumonias. First, we will perform a comprehensive and longitudinal phenotyping of MAIT cells during viral pneumonia-induced ARDS. Next, we will decipher the mechanisms leading to the observed phenotypes. Last, we will attempt to bring the grounds for potential future MAIT cell-based therapy to fight ARDS.