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Human MAIT cells show metabolic quiescence with rapid glucose‐dependent upregulation of granzyme B upon stimulation

Mucosal‐associated invariant T (MAIT) cells are a well‐characterized innate‐like T cell population abundant in the human liver, peripheral tissues and blood. MAIT cells serve in the first line of defense against infections, through engagement of their T cell receptor, which recognizes microbial meta...

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Autores principales: Zinser, Madeleine E, Highton, Andrew J, Kurioka, Ayako, Kronsteiner, Barbara, Hagel, Joachim, Leng, Tianqi, Marchi, Emanuele, Phetsouphanh, Chansavath, Willberg, Chris B, Dunachie, Susanna J, Klenerman, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055666/
https://www.ncbi.nlm.nih.gov/pubmed/29423939
http://dx.doi.org/10.1111/imcb.12020
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author Zinser, Madeleine E
Highton, Andrew J
Kurioka, Ayako
Kronsteiner, Barbara
Hagel, Joachim
Leng, Tianqi
Marchi, Emanuele
Phetsouphanh, Chansavath
Willberg, Chris B
Dunachie, Susanna J
Klenerman, Paul
author_facet Zinser, Madeleine E
Highton, Andrew J
Kurioka, Ayako
Kronsteiner, Barbara
Hagel, Joachim
Leng, Tianqi
Marchi, Emanuele
Phetsouphanh, Chansavath
Willberg, Chris B
Dunachie, Susanna J
Klenerman, Paul
author_sort Zinser, Madeleine E
collection PubMed
description Mucosal‐associated invariant T (MAIT) cells are a well‐characterized innate‐like T cell population abundant in the human liver, peripheral tissues and blood. MAIT cells serve in the first line of defense against infections, through engagement of their T cell receptor, which recognizes microbial metabolites presented on MR1, and through cytokine‐mediated triggering. Typically, they show a quiescent memory phenotype but can undergo rapid upregulation of effector functions including cytolysis upon stimulation. T cells profoundly change their cellular metabolism during their maturation and activation. We sought to determine how MAIT cell metabolism may facilitate both the long‐term memory phase in tissue and the transition to rapid effector function. Here, we show, by flow cytometric metabolism assays and extracellular flux analysis that, despite an effector‐memory profile, human MAIT cells are metabolically quiescent in a resting state comparable to naïve and central memory T cells. Upon stimulation, they rapidly increase uptake of glucose and show a concomitant upregulation of the effector molecules notably granzyme B, which is impaired by inhibition of glycolysis with 2‐deoxyglucose. These findings suggest that MAIT cells share some metabolic characteristics of both resting and effector T cell subsets, with a rapid transition upon triggering. Metabolic programming of this cell type may be of interest in understanding and modulating their function in infectious diseases and cancer.
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spelling pubmed-60556662018-07-23 Human MAIT cells show metabolic quiescence with rapid glucose‐dependent upregulation of granzyme B upon stimulation Zinser, Madeleine E Highton, Andrew J Kurioka, Ayako Kronsteiner, Barbara Hagel, Joachim Leng, Tianqi Marchi, Emanuele Phetsouphanh, Chansavath Willberg, Chris B Dunachie, Susanna J Klenerman, Paul Immunol Cell Biol Short Communication Mucosal‐associated invariant T (MAIT) cells are a well‐characterized innate‐like T cell population abundant in the human liver, peripheral tissues and blood. MAIT cells serve in the first line of defense against infections, through engagement of their T cell receptor, which recognizes microbial metabolites presented on MR1, and through cytokine‐mediated triggering. Typically, they show a quiescent memory phenotype but can undergo rapid upregulation of effector functions including cytolysis upon stimulation. T cells profoundly change their cellular metabolism during their maturation and activation. We sought to determine how MAIT cell metabolism may facilitate both the long‐term memory phase in tissue and the transition to rapid effector function. Here, we show, by flow cytometric metabolism assays and extracellular flux analysis that, despite an effector‐memory profile, human MAIT cells are metabolically quiescent in a resting state comparable to naïve and central memory T cells. Upon stimulation, they rapidly increase uptake of glucose and show a concomitant upregulation of the effector molecules notably granzyme B, which is impaired by inhibition of glycolysis with 2‐deoxyglucose. These findings suggest that MAIT cells share some metabolic characteristics of both resting and effector T cell subsets, with a rapid transition upon triggering. Metabolic programming of this cell type may be of interest in understanding and modulating their function in infectious diseases and cancer. John Wiley and Sons Inc. 2018-03-09 2018-07 /pmc/articles/PMC6055666/ /pubmed/29423939 http://dx.doi.org/10.1111/imcb.12020 Text en © 2018 The AuthorsImmunology and Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Immunology Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
Zinser, Madeleine E
Highton, Andrew J
Kurioka, Ayako
Kronsteiner, Barbara
Hagel, Joachim
Leng, Tianqi
Marchi, Emanuele
Phetsouphanh, Chansavath
Willberg, Chris B
Dunachie, Susanna J
Klenerman, Paul
Human MAIT cells show metabolic quiescence with rapid glucose‐dependent upregulation of granzyme B upon stimulation
title Human MAIT cells show metabolic quiescence with rapid glucose‐dependent upregulation of granzyme B upon stimulation
title_full Human MAIT cells show metabolic quiescence with rapid glucose‐dependent upregulation of granzyme B upon stimulation
title_fullStr Human MAIT cells show metabolic quiescence with rapid glucose‐dependent upregulation of granzyme B upon stimulation
title_full_unstemmed Human MAIT cells show metabolic quiescence with rapid glucose‐dependent upregulation of granzyme B upon stimulation
title_short Human MAIT cells show metabolic quiescence with rapid glucose‐dependent upregulation of granzyme B upon stimulation
title_sort human mait cells show metabolic quiescence with rapid glucose‐dependent upregulation of granzyme b upon stimulation
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055666/
https://www.ncbi.nlm.nih.gov/pubmed/29423939
http://dx.doi.org/10.1111/imcb.12020
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