Research Publications


Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8(+) T cells

Bachem, A; Makhlouf, C; Binger, KJ; De Souza, DP; Tull, D; Hochheiser, K; Whitney, PG; Fernandez-Ruiz, D; Dahling, S; Kastenmuller, W; Jonsson, J; Gressier, E; Lew, AM; Perdomo, C; Kupz, A; Figgett, W; Mackay, F; Oleshansky, M; Russ, BE; Parish, IA; Kallies, A; McConville, MJ; Turner, SJ; Gebhardt, T; Bedoui, S
Journal Article
Interactions with the microbiota influence many aspects of immunity, including immune cell development, differentiation, and function. Here, we examined the impact of the microbiota on CD8(+) T cell memory. Antigen-activated CD8(+) T cells transferred into germ-free mice failed to transition into long-lived memory cells and had transcriptional impairments in core genes associated with oxidative metabolism. The microbiota-derived short-chain fatty acid (SCFA) butyrate promoted cellular metabolism, enhanced memory potential of activated CD8(+) T cells, and SCFAs were required for optimal recall responses upon antigen re-encounter. Mechanistic experiments revealed that butyrate uncoupled the tricarboxylic acid cycle from glycolytic input in CD8(+) T cells, which allowed preferential fueling of oxidative phosphorylation through sustained glutamine utilization and fatty acid catabolism. Our findings reveal a role for the microbiota in promoting CD8(+) T cell long-term survival as memory cells and suggest that microbial metabolites guide the metabolic rewiring of activated CD8(+) T cells to enable this transition.
Cell Press
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Creation Date 2019-07-17 01:31:53 Last Modified 2019-08-23 02:43:52