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Microbiota-Derived Short-Chain Fatty Acids Promote the Memory Potential of Antigen-Activated CD8+ T Cells.

Bachem, Annabell; Makhlouf, Christina; Binger, Katrina J; de Souza, David P; Tull, Deidra; Hochheiser, Katharina; Whitney, Paul G; Fernandez-Ruiz, Daniel; Dähling, Sabrina; Kastenmüller, Wolfgang; Jönsson, Johanna; Gressier, Elise; Lew, Andrew M; Perdomo, Carolina; Kupz, Andreas; Figgett, William; Mackay, Fabienne; Oleshansky, Moshe; Russ, Brendan E; Parish, Ian A; Kallies, Axel; McConville, Malcolm J; Turner, Stephen J; Gebhardt, Thomas; Bedoui, Sammy.
Immunity; 51(2): 285-297.e5, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31272808
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.
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