Mucosal-associated invariant and ?? T cell subsets respond to initial Mycobacterium tuberculosis infection.

ABSTRACT: Innate immune responses that control early Mtb infection are poorly understood, but understanding these responses may inform vaccination and immunotherapy strategies. Innate T cells that respond to conserved bacterial ligands such as mucosal-associated invariant T (MAIT) and ?? T cells are prime candidates to mediate these early innate responses but have not been examined in subjects who have been recently exposed to Mtb. We recruited a cohort living in the same household with an active tuberculosis (TB) case and examined the abundance and functional phenotypes of 3 innate T cell populations reactive to M. tuberculosis: ?? T, invariant NK T (iNKT), and MAIT cells. Both MAIT and ?? T cells from subjects with Mtb exposure display ex vivo phenotypes consistent with recent activation. However, both MAIT and ?? T cell subsets have distinct response profiles, with CD4+ MAIT and ?? T cells accumulating after infection. Examination of exposed but uninfected contacts demonstrates that resistance to initial infection is accompanied by robust MAIT cell CD25 expression and granzyme B production coupled with a depressed CD69 and IFN? response. Finally, we demonstrate that MAIT cell abundance and function correlate with the abundance of specific gut microbes, suggesting that responses to initial infection may be modulated by the intestinal microbiome.

SUBMITTER: Vorkas CK 

PROVIDER: S-EPMC6237486 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature