Efficient 5-OP-RU-induced enrichment of Mucosal-associated invariant T cells in the murine lung does not enhance control of aerosol <i>Mycobacterium tuberculosis</i> infection

Abstract Mucosal-associated invariant T (MAIT) cells are an innate-like T cell subset in mammals that recognize microbial vitamin B metabolites presented by the evolutionarily conserved MHC I-related molecule MR1. Emerging data suggest that MAIT cells may be an attractive target for vaccine-induced protection against bacterial infections because of their rapid cytotoxic responses at mucosal services to a widely conserved bacterial ligand. In this study, we tested whether a MAIT cell priming strategy could protect against aerosol Mycobacterium tuberculosis ( Mtb ) infection in mice. Intranasal co-stimulation with the lipopeptide TLR 2/6 agonist, Pam2Cys (P2C), and the synthetic MR1 ligand, 5-OP-RU, resulted in robust expansion of MAIT cells in lung. Although MAIT cell priming significantly enhanced MAIT cell activation and expansion early after Mtb challenge, these MAIT cells did not restrict Mtb bacterial load. MAIT cells were depleted later in infection, with decreased detection of granzyme B + and IFNγ + MAIT cells relative to uninfected P2C/5-OP-RU-treated mice. Decreasing the infectious inoculum, varying the time between priming and aerosol infection, and testing MAIT cell priming in NOS2 deficient mice all failed to reveal an effect of P2C/5-OP-RU induced MAIT cells on Mtb control. We conclude that intranasal MAIT cell priming in mice induces early MAIT cell activation and expansion after Mtb exposure, without attenuating M. tuberculosis growth, suggesting that Mtb evades MAIT cell-dependent immunity.