1. Memory CD8 + T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection.
- Author
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Balmer ML, Ma EH, Thompson AJ, Epple R, Unterstab G, Lötscher J, Dehio P, Schürch CM, Warncke JD, Perrin G, Woischnig AK, Grählert J, Löliger J, Assmann N, Bantug GR, Schären OP, Khanna N, Egli A, Bubendorf L, Rentsch K, Hapfelmeier S, Jones RG, and Hess C
- Subjects
- Acetates blood, Acetates immunology, Animals, Anti-Inflammatory Agents immunology, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes immunology, Female, Humans, Male, Mice, Mice, Inbred C57BL, Acetates metabolism, Anti-Inflammatory Agents metabolism, CD8-Positive T-Lymphocytes metabolism
- 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., Competing Interests: Declaration of Interests The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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