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JCI Insight. 2018 Oct 4;3(19). pii: 121899. doi: 10.1172/jci.insight.121899. [Epub ahead of print]

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

Author information

1
Division of Infectious Diseases, Weill Cornell Medicine (WCM), New York, New York, USA.
2
Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center (MSKCC), New York, New York, USA.
3
Clinical and Translational Science Center, WCM, New York, New York, USA.
4
Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
5
Department of Bioengineering, University of Massachusetts, Dartmouth, North Dartmouth, Massachusetts, USA.
6
Immune Monitoring Core Facility, Ludwig Center for Cancer Immunotherapy, Sloan Kettering Institute, MSKCC, New York, New York, USA.
7
GHESKIO Centers, Port-au-Prince, Haiti.
8
Center for Global Health, WCM, New York, New York, USA.
9
Division of Infectious Diseases, MSKCC, New York, New York, USA.

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 γδ 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: γδ T, invariant NK T (iNKT), and MAIT cells. Both MAIT and γδ T cells from subjects with Mtb exposure display ex vivo phenotypes consistent with recent activation. However, both MAIT and γδ T cell subsets have distinct response profiles, with CD4+ MAIT and γδ 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 IFNγ 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.

KEYWORDS:

Immunology; Infectious disease; Innate immunity; Tuberculosis

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