Memory CD8+ T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection.

Memory CD8+ T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection.
Cell Metab. 2020 Jul 24;:
Authors: Balmer ML, Ma EH, Thompson A, 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, Hess C
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 pr...

Source: Cell Metabolism - July 23, 2020 Category: Cytology Authors: Balmer ML, Ma EH, Thompson A, 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, Hess Tags: Cell Metab Source Type: research