First Author | Bachem A | Year | 2019 |
Journal | Immunity | Volume | 51 |
Issue | 2 | Pages | 285-297.e5 |
PubMed ID | 31272808 | Mgi Jnum | J:282380 |
Mgi Id | MGI:6380753 | Doi | 10.1016/j.immuni.2019.06.002 |
Citation | Bachem A, et al. (2019) Microbiota-Derived Short-Chain Fatty Acids Promote the Memory Potential of Antigen-Activated CD8(+) T Cells. Immunity 51(2):285-297.e5 |
abstractText | 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. |