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

abstract

  • 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.

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

publication date

  • 2019