Memory CD8+ T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection.
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Authors
Balmer, Maria L
Ma, Eric H
Epple, Raja
Unterstab, Gunhild
Lötscher, Jonas
Dehio, Philippe
Schürch, Christian M
Warncke, Jan D
Perrin, Gaëlle
Woischnig, Anne-Kathrin
Grählert, Jasmin
Löliger, Jordan
Assmann, Nadine
Bantug, Glenn R
Schären, Olivier P
Khanna, Nina
Egli, Adrian
Bubendorf, Lukas
Rentsch, Katharina
Hapfelmeier, Siegfried
Jones, Russell G
Hess, Christoph
Publication Date
2020-09-01Journal Title
Cell Metab
ISSN
1550-4131
Publisher
Elsevier BV
Volume
32
Issue
3
Pages
457-467.e5
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Balmer, M. L., Ma, E. H., Thompson, A., Epple, R., Unterstab, G., Lötscher, J., Dehio, P., et al. (2020). Memory CD8+ T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection.. Cell Metab, 32 (3), 457-467.e5. https://doi.org/10.1016/j.cmet.2020.07.004
Abstract
Serum acetate increases upon systemic infection. Acutely, assimilation of acetate expands the capacity of memory CD8+ T cells to produce IFN-γ. Whether acetate modulates memory CD8+ T cell metabolism and function during pathogen re-encounter remains unexplored. Here we show that at sites of infection, high acetate concentrations are being reached, yet memory CD8+ T cells shut down the acetate assimilating enzymes ACSS1 and ACSS2. Acetate, being thus largely excluded from incorporation into cellular metabolic pathways, now had different effects, namely (1) directly activating glutaminase, thereby augmenting glutaminolysis, cellular respiration, and survival, and (2) suppressing TCR-triggered calcium flux, and consequently cell activation and effector cell function. In vivo, high acetate abundance at sites of infection improved pathogen clearance while reducing immunopathology. This indicates that, during different stages of the immune response, the same metabolite-acetate-induces distinct immunometabolic programs within the same cell type.
Identifiers
External DOI: https://doi.org/10.1016/j.cmet.2020.07.004
This record's URL: https://www.repository.cam.ac.uk/handle/1810/308104
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
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