Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8+ T cells

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, and Bedoui, Sammy (2019) Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8+ T cells. Immunity, 51. pp. 285-297.

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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.

Item ID: 59101
Item Type: Article (Research - C1)
ISSN: 1097-4180
Keywords: CD8+ T cells; memory differentiation; microbiota; short-chain fatty acids; butyrate; T cell metabolism; fatty acid oxidation
Copyright Information: © 2019 Elsevier Inc.
Funders: National Medical Research Council of Australia, Sylvia and Charles Viertel Charitable Foundation (SCVCF), Merck KGaA, German Research Council (GRC)
Date Deposited: 02 Aug 2019 04:44
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 33%
06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060599 Microbiology not elsewhere classified @ 33%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110399 Clinical Sciences not elsewhere classified @ 34%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 50%
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