Early MR1 upregulation on antigen-presenting cells following influenza A virus immunization: implications for co-infections and superinfections 3103

Abstract Description Influenza A viruses (IAVs) remain a global health threat due to their high mutation rates, which complicate vaccine efficacy. Targeting mucosa-associated invariant T (MAIT) cells, an innate-like T cell subset, has been linked to improved vaccine strategies. We investigated the expression of MHC class I-related protein 1 (MR1), essential for MAIT cell activation against bacterial pathogens, on antigen-presenting cells in C57BL/6 mice immunized with A/Puerto Rico/8/1934 (PR8) (H1N1) and A/Hong Kong/1/1968 (HK) (H3N2) IAV strains. Flow cytometry revealed significant MR1 upregulation on F4/80+ macrophages and CD11c+ dendritic cells in the peritoneal cavity, lungs, spleen, and blood at 24 hours and sustained for at least 3 days. MR1 upregulation was notably reduced with heat-inactivated PR8, highlighting a requirement for active viral replication. In vivo administration of poly(I:C), but not Imiquimod, recapitulated IAV immunization, suggesting a role for TLR3 triggering in this setting. In human cell cultures, MR1 upregulation was accompanied by MHC I downregulation, indicating the selectivity of the observed phenomenon for MR1. Additionally, PR8 exposure activated primary human MAIT cells, as evidenced by CD38 and HLA-DR expression. Since MR1 presents bacterial metabolites to MAIT cells, eliciting antibacterial responses, we propose that anti-IAV vaccination not only protects against these viruses but also primes the immune system to combat secondary bacterial infections. Topic Categories Mucosal and Regional Immunology (MUC)