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.

中文翻译：

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微生物群衍生的短链脂肪酸可提高抗原激活的CD8 + T细胞的记忆潜能。

与微生物群的相互作用会影响免疫力的许多方面，包括免疫细胞的发育，分化和功能。在这里，我们检查了微生物群对CD8 + T细胞记忆的影响。转移到无菌小鼠中的抗原激活的CD8 + T细胞未能转变为长寿的记忆细胞，并且在与氧化代谢相关的核心基因中存在转录损伤。微生物群来源的短链脂肪酸（SCFA）丁酸酯可促进细胞代谢，增强活化的CD8 + T细胞的记忆潜能，而SCFA则是抗原再次遇到后能产生最佳召回反应的必需条件。机理实验表明，丁酸酯可将三羧酸循环与CD8 + T细胞中的糖酵解输入解耦，通过持续利用谷氨酰胺和脂肪酸分解代谢，可以优先为氧化磷酸化提供燃料。我们的发现揭示了微生物群在促进CD8 + T细胞作为记忆细胞的长期存活中的作用，并表明微生物代谢产物指导活化的CD8 + T细胞的代谢重新连接，以实现这种过渡。