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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
John Wiley & Sons Australia, Ltd
2018
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| _version_ | 1826271289147392000 |
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| author | Zinser, ME Highton, AJ Kurioka, A Kronsteiner, B Hagel, J Leng, T Marchi, E Phetsouphanh, C Willberg, CB Dunachie, SJ Klenerman, P |
| author_facet | Zinser, ME Highton, AJ Kurioka, A Kronsteiner, B Hagel, J Leng, T Marchi, E Phetsouphanh, C Willberg, CB Dunachie, SJ Klenerman, P |
| author_sort | Zinser, ME |
| collection | OXFORD |
| 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 up-regulation 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. This article is protected by copyright. All rights reserved. |
| first_indexed | 2024-03-06T21:54:20Z |
| format | Journal article |
| id | oxford-uuid:4c661ba8-884c-465d-9d28-7cfff098ce08 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:54:20Z |
| publishDate | 2018 |
| publisher | John Wiley & Sons Australia, Ltd |
| record_format | dspace |
| spelling | oxford-uuid:4c661ba8-884c-465d-9d28-7cfff098ce082022-03-26T15:49:14ZHuman MAIT cells show metabolic quiescence with rapid glucose-dependent upregulation of granzyme B upon stimulationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4c661ba8-884c-465d-9d28-7cfff098ce08EnglishSymplectic Elements at OxfordJohn Wiley & Sons Australia, Ltd2018Zinser, MEHighton, AJKurioka, AKronsteiner, BHagel, JLeng, TMarchi, EPhetsouphanh, CWillberg, CBDunachie, SJKlenerman, PMucosal-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 up-regulation 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. This article is protected by copyright. All rights reserved. |
| spellingShingle | Zinser, ME Highton, AJ Kurioka, A Kronsteiner, B Hagel, J Leng, T Marchi, E Phetsouphanh, C Willberg, CB Dunachie, SJ Klenerman, P 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 |
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