Journal article
The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages
J Schulthess, S Pandey, M Capitani, KC Rue-Albrecht, I Arnold, F Franchini, A Chomka, NE Ilott, DGW Johnston, E Pires, J McCullagh, SN Sansom, CV Arancibia-Cárcamo, HH Uhlig, F Powrie
Immunity | CELL PRESS | Published : 2019
Abstract
Host microbial cross-talk is essential to maintain intestinal homeostasis. However, maladaptation of this response through microbial dysbiosis or defective host defense toward invasive intestinal bacteria can result in chronic inflammation. We have shown that macrophages differentiated in the presence of the bacterial metabolite butyrate display enhanced antimicrobial activity. Butyrate-induced antimicrobial activity was associated with a shift in macrophage metabolism, a reduction in mTOR kinase activity, increased LC3-associated host defense and anti-microbial peptide production in the absence of an increased inflammatory cytokine response. Butyrate drove this monocyte to macrophage differ..
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Awarded by SNS Nordic Forest Research
Funding Acknowledgements
We thank all volunteers and blood donors for participation in this study. We thank Sebastian Rogatti for technical assistance, Helen Ferry and Jonathan Webber for flow cytometry cell sorting, and the staff of our animal houses. We acknowledge the contribution of the BRC Gastrointestinal biobank (11/YH/0020, 16/YH/0247), supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). This work was supported by the Wellcome Trust UK (095688/Z/11/Z: F.P., D.G.W.J., and A.C.), the BBSRC (BB/I005609/1: FP, CVA-C, JS), the Leona M. and Harry B. Helmsley Charitable Trust (FP, HHU, JS, MC), the Kennedy Trust for Rheumatology Research (SNS, K.C.R-A. and N.E.I.), CRUK grant (OCRC-DPHIL13-FF: FF) and the Crohn's & Colitis Foundation of America (HHU, FP and SP). Salmonella enterica serovar Typhimurium (S. Typhimurium)-expressing GFP was kindly provided by D. Holden (Imperial College, University of London, UK) and adherent-invasive E. coli reference strain LF82 (AIEC) by A. Darfeuille-Michaud. The graphical abstract was prepared including a graphic element from Les Laboratoires Servier. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.