Poster Presentation CD1-MR1 2024

MAIT cell activation and dynamics associated with Influenza virus infection (#200)

Apurwa Trivedi 1 , Mauro Gaya 1
  1. Centre d'Immunologie de Marseille Luminy (Marseille-Luminy Immunology Center) CIML, Marseille, BOUCHES-DU-RHôNE, France

Mucosal-associated invariant T (MAIT) cells recognize vitamin metabolites derived from bacteria through their semi-invariant TCR and mediate anti-bacterial functions. Emerging evidence indicates that MAIT cells get activated during viral infection without TCR engagement. However, the mechanisms through which this TCR-independent MAIT cell activation mediates host protection remain unclear.  In this study, we highlight how MAIT cells straddle the line between innate and adaptive immunity. We present a multifaceted role of MAIT cells in the case of murine respiratory viral infection with Influenza virus. We found that MAIT cells produce an early wave of IL-17 that is crucial for the influx of innate immune cells at the site of infection. Upon performing single-cell RNA sequencing of MAIT cells post-infection, we found that the pro-inflammatory functions of MAIT cells are linked to the upregulation of antiviral interferon-related genes. In the context of adaptive immunity, our findings indicate that MAIT cells are required for the secretion of Influenza-specific IgA antibodies, but not IgG or IgM antibodies, into the bronchoalveolar space. Remarkably, this effect is not due to impaired production of IgA-secreting cells but due to an impaired migration of these cells towards the lung mucosa in the absence of the MAIT cell-IL-17 axis. In conclusion, here we report novel functions of MAIT cells that go beyond recognition of bacteria-derived metabolites through the exertion of an early and robust production of IL-17 in response to viral infection.