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Mucosal-associated invariant and γδ T cell subsets respond to initial Mycobacterium tuberculosis infection
Charles Kyriakos Vorkas, … , Daniel W. Fitzgerald, Michael S. Glickman
Charles Kyriakos Vorkas, … , Daniel W. Fitzgerald, Michael S. Glickman
Published October 4, 2018
Citation Information: JCI Insight. 2018;3(19):e121899. https://doi.org/10.1172/jci.insight.121899.
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Research Article Immunology Infectious disease

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

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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.

Authors

Charles Kyriakos Vorkas, Matthew F. Wipperman, Kelin Li, James Bean, Shakti K. Bhattarai, Matthew Adamow, Phillip Wong, Jeffrey Aubé, Marc Antoine Jean Juste, Vanni Bucci, Daniel W. Fitzgerald, Michael S. Glickman

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Figure 1

γδ T cells respond early to Mycobacterium tuberculosis infection.

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γδ T cells respond early to Mycobacterium tuberculosis infection.
(A) De...
(A) Density plots demonstrating the gating strategy for γδ T cells in 1 healthy Haitian donor: left panel is gated on live cells, and right panel is gated on live CD3+TCRγδ+ cells. (B) TCRγδ staining in CD4+ T cells (left) with IGRA stratification (right) in community controls (green) and household contacts (purple). Color coding applies to all panels. Data in B–F represent mean ± SD. (C) Relative abundance of TCRγ subsets within their respective T cell subsets (left) with IGRA stratification (right). (D) PD-1 staining in CD4+ γδ T cells after 15 hours of rest (left) or anti-CD3/CD28 stimulation (right). Groups were compared by 2-tailed unpaired t test in A–D with significance level of P < 0.05. CD4+ γδ T cell PD-1 staining before or after anti-CD3/CD28 activation in IGRA+ community controls (E) and contacts (F). Groups were compared by 2-tailed paired t test in E and F with significance level of P < 0.05. *P < 0.05, **P < 0.005, ****P < 0.0001. IGRA, IFNγ release assay

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