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Mucosal Immunol. 2018 Jul;11(4):1060-1070. doi: 10.1038/s41385-018-0020-9. Epub 2018 May 9.

Modulation of bacterial metabolism by the microenvironment controls MAIT cell stimulation.

Author information

1
Experimental Immunology, Department of Biomedicine, University and University Hospital Basel, 4031, Basel, Switzerland.
2
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, 138648, Singapore.
3
Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich, Switzerland.
4
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, 06510, USA.
5
Applied Microbiology Research, Department of Biomedicine, University and University Hospital Basel, 4031, Basel, Switzerland.
6
Clinical Microbiology, University Hospital Basel, 4031, Basel, Switzerland.
7
Department of Food and Drug, University of Parma, Parma, Italy.
8
Department of Gastroenterology, University Hospital, Basel, Switzerland.
9
Experimental Immunology, Department of Biomedicine, University and University Hospital Basel, 4031, Basel, Switzerland. lucia.mori@unibas.ch.
10
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, 138648, Singapore. lucia.mori@unibas.ch.
11
Experimental Immunology, Department of Biomedicine, University and University Hospital Basel, 4031, Basel, Switzerland. gennaro.delibero@unibas.ch.
12
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, 138648, Singapore. gennaro.delibero@unibas.ch.

Abstract

Mucosal-associated invariant T (MAIT) cells are abundant innate-like T lymphocytes in mucosal tissues and recognize a variety of riboflavin-related metabolites produced by the microbial flora. Relevant issues are whether MAIT cells are heterogeneous in the colon, and whether the local environment influences microbial metabolism thereby shaping MAIT cell phenotypes and responses. We found discrete MAIT cell populations in human colon, characterized by the diverse expression of transcription factors, cytokines and surface markers, indicative of activated and precisely controlled lymphocyte populations. Similar phenotypes were rare among circulating MAIT cells and appeared when circulating MAIT cells were stimulated with the synthetic antigens 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil, and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil. Furthermore, bacteria grown in colon-resembling conditions with low oxygen tension and harvested at stationary growth phase, potently activated human MAIT cells. The increased activation correlated with accumulation of the above antigenic metabolites as indicated by mass spectrometry. Thus, the colon environment contributes to mucosal immunity by directly affecting bacterial metabolism, and indirectly controlling the stimulation and differentiation of MAIT cells.

PMID:
29743612
DOI:
10.1038/s41385-018-0020-9
[Indexed for MEDLINE]

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