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

Authors:

• 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

Details:

Immunity, Volume 51, Issue 2, 2019-08-20

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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.