Microbiota-derived butyrate promotes cellular metabolism and memory potential of antigen-activated CD8+ T cells

Abstract

Abstract Microbiota modulate the immune system and recent studies suggest a functional relationship between microbiota, its metabolites and CD8+ T cells, but whether this link is also relevant for CD8+ T cell memory is unclear. We show that antigen-activated CD8+ T cells transferred into germ-free mice had transcriptional impairments in oxidative metabolism and failed to transition into memory cells with enhanced recall capacity. Conversely, the microbiotaderived metabolite butyrate promoted memory potential and secondary recall responses of activated CD8+ T cells. This was accompanied by metabolic rewiring of the T cells and uncoupling of the tricarboxylic acid cycle from glycolytic input, enabling preferential fuelling of enhanced oxidative phosphorylation through glutamine utilization and fatty acid catabolism. As such energetic adaptions promote memory T cell differentiation, our findings uncover an important role for microbiota-derived butyrate in rewiring the metabolism of activated CD8+ T cells in support of their long-term survival as memory cells.