Efficient 5-OP-RU-Induced Enrichment of Mucosa-Associated Invariant T Cells in the Murine Lung Does Not Enhance Control of Aerosol Mycobacterium tuberculosis Infection

Mucosa-associated invariant T (MATT) cells are an innate-like T cell subset in mammals that recognize microbial vitamin B metabolites presented by the evolutionarily conserved major histocompatibility complex class I (MHC I)-related molecule, MR1. Emerging data suggest that MATT 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 MATT cell priming strategy could protect against aerosol Mycobacterium tuberculosis infection in mice. Intranasal costimulation with the lipopeptide Toll-like receptor (TLR)2/6 agonist, Pam2Cys (P2C), and the synthetic MR1 ligand, 5-OP-RU, resulted in robust expansion of MATT cells in the lung. Although MATT cell priming significantly enhanced MATT cell activation and expansion early after M. tuberculosis challenge, these MATT cells did not restrict M. tuberculosis bacterial load. MATT cells were depleted by the onset of the adaptive immune response, with decreased detection of granzyme B+ and gamma interferon (IFN-gamma)(+) MATT cells relative to that in uninfected P2C/5-OP-RU-treated mice. Decreasing the infectious inoculum, varying the time between priming and aerosol infection, and testing MATT cell priming in nitric oxide synthase 2 (NOS2)-deficient mice all failed to reveal an effect of P2C/5-OP-RU-induced MATT cells on M. tuberculosis control. We conclude that intranasal MATT cell priming in mice induces early MATT cell activation and expansion after M. tuberculosis exposure, without attenuating M. tuberculosis growth, suggesting that MATT cell enrichment in the lung is not sufficient to control M. tuberculosis infection.

Automated summary

This study tested the impact of a MATT cell priming strategy on mice infected with aerosol Mycobacterium tuberculosis and found that although MATT cells could rapidly activate and expand in the lung after M. tuberculosis exposure, they were not able to restrict M. tuberculosis growth.