Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signals

Chen, Z., Wang, H., D'Souza, C., Sun, S., Kostenko, L., Eckle, S. B. G., Meehan, B. S., Jackson, D. C., Strugnell, R. A., Cao, H., Wang, N., Fairlie, D. P., Liu, L., Godfrey, D. I., Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, McCluskey, J. and Corbett, A. J. 2017. Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signals. Mucosal Immunology 10 (1) , pp. 58-68. 10.1038/mi.2016.39

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Abstract

Despite recent breakthroughs in identifying mucosal-associated invariant T (MAIT) cell antigens (Ags), the precise requirements for in vivo MAIT cell responses to infection remain unclear. Using major histocompatibility complex–related protein 1 (MR1) tetramers, the MAIT cell response was investigated in a model of bacterial lung infection employing riboflavin gene-competent and -deficient bacteria. MAIT cells were rapidly enriched in the lungs of C57BL/6 mice infected with Salmonella Typhimurium, comprising up to 50% of αβ-T cells after 1 week. MAIT cell accumulation was MR1-dependent, required Ag derived from the microbial riboflavin synthesis pathway, and did not occur in response to synthetic Ag, unless accompanied by a Toll-like receptor agonist or by co-infection with riboflavin pathway-deficient S. Typhimurium. The MAIT cell response was associated with their long-term accumulation in the lungs, draining lymph nodes and spleen. Lung MAIT cells from infected mice displayed an activated/memory phenotype, and most expressed the transcription factor retinoic acid–related orphan receptor γt. T-bet expression increased following infection. The majority produced interleukin-17 while smaller subsets produced interferon-γ or tumor necrosis factor, detected directly ex vivo. Thus the activation and expansion of MAIT cells coupled with their pro-inflammatory cytokine production occurred in response to Ags derived from microbial riboflavin synthesis and was augmented by co-stimulatory signals.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Nature Publishing Group
ISSN:	1933-0219
Date of First Compliant Deposit:	27 July 2017
Date of Acceptance:	19 March 2016
Last Modified:	05 Dec 2024 05:30
URI:	https://orca.cardiff.ac.uk/id/eprint/100003

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