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 Journal Article
| Authors: | Vorkas, C. K.; Levy, O.; Skular, M.; Li, K.; Aubé, J.; Glickman, M. S. |
| Article Title: | 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 |
| Abstract: | Mucosa-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 major histocompatibility complex class I (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 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 MAIT cells in the lung. Although MAIT cell priming significantly enhanced MAIT cell activation and expansion early after M. tuberculosis challenge, these MAIT cells did not restrict M. tuberculosis bacterial load. MAIT cells were depleted by the onset of the adaptive immune response, with decreased detection of granzyme B+ and gamma interferon (IFN-γ)+ MAIT 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 MAIT cell priming in nitric oxide synthase 2 (NOS2)-deficient mice all failed to reveal an effect of P2C/5-OP-RU-induced MAIT cells on M. tuberculosis control. We conclude that intranasal MAIT cell priming in mice induces early MAIT cell activation and expansion after M. tuberculosis exposure, without attenuating M. tuberculosis growth, suggesting that MAIT cell enrichment in the lung is not sufficient to control M. tuberculosis infection. © 2020 American Society for Microbiology. All Rights Reserved. |
| Keywords: | controlled study; unclassified drug; disease course; drug efficacy; nonhuman; t lymphocyte; mouse; animal experiment; animal model; in vivo study; in vitro study; granzyme b; gamma interferon; innate immunity; adaptive immunity; inducible t cell costimulator ligand; cell activation; data analysis software; cell expansion; toll like receptor 2; tuberculosis; inoculation; inducible nitric oxide synthase; mediastinum lymph node; bacterial growth; lung tuberculosis; lung alveolus cell; aerosol; tuberculostatic agent; bacterial load; polypeptide antibiotic agent; toll like receptor 6; female; priority journal; article; mait cells; 5 op ru; p2c; lipopeptide 5 op ru; lipopeptide pam 2 cys; mucosal-associated invariant t cell |
| Journal Title: | Infection and Immunity |
| Volume: | 89 |
| Issue: | 1 |
| ISSN: | 0019-9567 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2021-01-01 |
| Start Page: | e00524-20 |
| Language: | English |
| DOI: | 10.1128/iai.00524-20 |
| PUBMED: | 33077620 |
| PROVIDER: | scopus |
| PMCID: | PMC7927919 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2021 -- Source: Scopus |
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