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Divergent metabolic programmes control two populations of MAIT cells that protect the lung
Although mucosal-associated invariant T (MAIT) cells provide rapid, innate-like responses, they are not pre-set, and memory-like responses have been described for MAIT cells following infections. The importance of metabolism for controlling these responses, however, is unknown. Here, following pulmo...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10264248/ https://www.ncbi.nlm.nih.gov/pubmed/37231163 http://dx.doi.org/10.1038/s41556-023-01152-6 |
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author | Riffelmacher, Thomas Paynich Murray, Mallory Wientjens, Chantal Chandra, Shilpi Cedillo-Castelán, Viankail Chou, Ting-Fang McArdle, Sara Dillingham, Christopher Devereaux, Jordan Nilsen, Aaron Brunel, Simon Lewinsohn, David M. Hasty, Jeff Seumois, Gregory Benedict, Christopher A. Vijayanand, Pandurangan Kronenberg, Mitchell |
author_facet | Riffelmacher, Thomas Paynich Murray, Mallory Wientjens, Chantal Chandra, Shilpi Cedillo-Castelán, Viankail Chou, Ting-Fang McArdle, Sara Dillingham, Christopher Devereaux, Jordan Nilsen, Aaron Brunel, Simon Lewinsohn, David M. Hasty, Jeff Seumois, Gregory Benedict, Christopher A. Vijayanand, Pandurangan Kronenberg, Mitchell |
author_sort | Riffelmacher, Thomas |
collection | PubMed |
description | Although mucosal-associated invariant T (MAIT) cells provide rapid, innate-like responses, they are not pre-set, and memory-like responses have been described for MAIT cells following infections. The importance of metabolism for controlling these responses, however, is unknown. Here, following pulmonary immunization with a Salmonella vaccine strain, mouse MAIT cells expanded as separate CD127(−)Klrg1(+) and CD127(+)Klrg1(−) antigen-adapted populations that differed in terms of their transcriptome, function and localization in lung tissue. These populations remained altered from steady state for months as stable, separate MAIT cell lineages with enhanced effector programmes and divergent metabolism. CD127(+) MAIT cells engaged in an energetic, mitochondrial metabolic programme, which was critical for their maintenance and IL-17A synthesis. This programme was supported by high fatty acid uptake and mitochondrial oxidation and relied on highly polarized mitochondria and autophagy. After vaccination, CD127(+) MAIT cells protected mice against Streptococcus pneumoniae infection. In contrast, Klrg1(+) MAIT cells had dormant but ready-to-respond mitochondria and depended instead on Hif1a-driven glycolysis to survive and produce IFN-γ. They responded antigen independently and participated in protection from influenza virus. These metabolic dependencies may enable tuning of memory-like MAIT cell responses for vaccination and immunotherapies. |
format | Online Article Text |
id | pubmed-10264248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102642482023-06-15 Divergent metabolic programmes control two populations of MAIT cells that protect the lung Riffelmacher, Thomas Paynich Murray, Mallory Wientjens, Chantal Chandra, Shilpi Cedillo-Castelán, Viankail Chou, Ting-Fang McArdle, Sara Dillingham, Christopher Devereaux, Jordan Nilsen, Aaron Brunel, Simon Lewinsohn, David M. Hasty, Jeff Seumois, Gregory Benedict, Christopher A. Vijayanand, Pandurangan Kronenberg, Mitchell Nat Cell Biol Article Although mucosal-associated invariant T (MAIT) cells provide rapid, innate-like responses, they are not pre-set, and memory-like responses have been described for MAIT cells following infections. The importance of metabolism for controlling these responses, however, is unknown. Here, following pulmonary immunization with a Salmonella vaccine strain, mouse MAIT cells expanded as separate CD127(−)Klrg1(+) and CD127(+)Klrg1(−) antigen-adapted populations that differed in terms of their transcriptome, function and localization in lung tissue. These populations remained altered from steady state for months as stable, separate MAIT cell lineages with enhanced effector programmes and divergent metabolism. CD127(+) MAIT cells engaged in an energetic, mitochondrial metabolic programme, which was critical for their maintenance and IL-17A synthesis. This programme was supported by high fatty acid uptake and mitochondrial oxidation and relied on highly polarized mitochondria and autophagy. After vaccination, CD127(+) MAIT cells protected mice against Streptococcus pneumoniae infection. In contrast, Klrg1(+) MAIT cells had dormant but ready-to-respond mitochondria and depended instead on Hif1a-driven glycolysis to survive and produce IFN-γ. They responded antigen independently and participated in protection from influenza virus. These metabolic dependencies may enable tuning of memory-like MAIT cell responses for vaccination and immunotherapies. Nature Publishing Group UK 2023-05-25 2023 /pmc/articles/PMC10264248/ /pubmed/37231163 http://dx.doi.org/10.1038/s41556-023-01152-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Riffelmacher, Thomas Paynich Murray, Mallory Wientjens, Chantal Chandra, Shilpi Cedillo-Castelán, Viankail Chou, Ting-Fang McArdle, Sara Dillingham, Christopher Devereaux, Jordan Nilsen, Aaron Brunel, Simon Lewinsohn, David M. Hasty, Jeff Seumois, Gregory Benedict, Christopher A. Vijayanand, Pandurangan Kronenberg, Mitchell Divergent metabolic programmes control two populations of MAIT cells that protect the lung |
title | Divergent metabolic programmes control two populations of MAIT cells that protect the lung |
title_full | Divergent metabolic programmes control two populations of MAIT cells that protect the lung |
title_fullStr | Divergent metabolic programmes control two populations of MAIT cells that protect the lung |
title_full_unstemmed | Divergent metabolic programmes control two populations of MAIT cells that protect the lung |
title_short | Divergent metabolic programmes control two populations of MAIT cells that protect the lung |
title_sort | divergent metabolic programmes control two populations of mait cells that protect the lung |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10264248/ https://www.ncbi.nlm.nih.gov/pubmed/37231163 http://dx.doi.org/10.1038/s41556-023-01152-6 |
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