Microbiota-Derived Short-Chain Fatty Acids Promote the Memory Potential of Antigen-Activated CD8 T Cells

A Bachem; C Makhlouf; KJ Binger; DP de Souza; D Tull; K Hochheiser; PG Whitney; D Fernandez-Ruiz; S Dähling; W Kastenmüller; J Jönsson; E Gressier; AM Lew; C Perdomo; A Kupz; W Figgett; F Mackay; M Oleshansky; BE Russ; IA Parish; A Kallies; MJ McConville; SJ Turner; T Gebhardt; S Bedoui

Journal article

Microbiota-Derived Short-Chain Fatty Acids Promote the Memory Potential of Antigen-Activated CD8 T Cells

A Bachem, C Makhlouf, KJ Binger, DP de Souza, D Tull, K Hochheiser, PG Whitney, D Fernandez-Ruiz, S Dähling, W Kastenmüller, J Jönsson, E Gressier, AM Lew, C Perdomo, A Kupz, W Figgett, F Mackay, M Oleshansky, BE Russ, IA Parish Show all

Immunity | CELL PRESS | Published : 2019

DOI: 10.1016/j.immuni.2019.06.002

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 tricarbo..

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University of Melbourne Researchers

Annabell Bachem Author

David de Souza Author

Andrew Lew Author

Fabienne Mackay Author

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Grants

Awarded by Sylvia and Charles Viertel Charitable Foundation

Funding Acknowledgements

We would like to thank Dr. Francis Carbone, Dr. William R. Heath, and Ms. Maike Effern for critical reading of the manuscript; Drs. Ian Trounce and Jonathan Crowston for expert advice; and Dr. Stefan Offermanns for generously providing Ffar2<SUP>-/-</SUP>; Ffar3<SUP>-/-</SUP> mice. The excellent technical expertise in breeding, maintaining, and manipulating SPF mice by the Doherty Bio-resources facility and GF mice by Cameron Mackenzie at the Walter & Eliza Hall Institute for Medical Research is gratefully acknowledged. Our research is supported by the National Health and Medical Research Council of Australia (APP1124815, APP1071916, APP1103895, and APP1154540), the Sylvia & Charles Viertel Charitable Foundation, a 350 th Anniversary Research Grant from Merck KgGA (Darmstadt, Germany), and the German Research Council (BA 5108/1-1).