Memory CD8(+) T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function

Maria Balmer, Eric Ma, Glenn Bantug, Jasmin Graehlert, S Pfister, T Glatter, A Jauch, Sarah Dimeloe, E Slack, P Dehio, M Krzyzaniak, C King, Anne-Valerie Burgener, Marco Fischer, Leyla Develioglu, Reka Belle, Mike Recher, V Bonilla, A MacPherson, S HapfelmeierR Jones, Christoph Hess

Research output: Contribution to journalArticlepeer-review

133 Citations (Scopus)


How systemic metabolic alterations during acute infections impact immune cell function remains poorly understood. We found that acetate accumulates in the serum within hours of systemic bacterial infections and that these increased acetate concentrations are required for optimal memory CD8(+) T cell function in vitro and in vivo. Mechanistically, upon uptake by memory CD8(+) T cells, stress levels of acetate expanded the cellular acetyl-coenzyme A pool via ATP citrate lyase and promoted acetylation of the enzyme GAPDH. This context-dependent post-translational modification enhanced GAPDH activity, catalyzing glycolysis and thus boosting rapid memory CD8(+) T cell responses. Accordingly, in a murine Listeria monocytogenes model, transfer of acetate-augmented memory CD8(+) T cells exerted superior immune control compared to control cells. Our results demonstrate that increased systemic acetate concentrations are functionally integrated by CD8(+) T cells and translate into increased glycolytic and functional capacity. The immune system thus directly relates systemic metabolism with immune alertness.
Original languageEnglish
Pages (from-to)1312-1324
Issue number6
Early online date17 May 2016
Publication statusPublished - 21 Jun 2016


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