Balmer, M. L. and Ma, E. H. and Bantug, G. R. and Grahlert, J. and Pfister, S. and Glatter, T. and Jauch, A. and Dimeloe, S. and Slack, E. and Dehio, P. and Krzyzaniak, M. A. and King, C. G. and Burgener, A. V. and Fischer, M. and Develioglu, L. and Belle, R. and Recher, M. and Bonilla, W. V. and Macpherson, A. J. and Hapfelmeier, S. and Jones, R. G. and Hess, C.. (2016) Memory CD8(+) T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function. Immunity, 44 (6). pp. 1312-1324.
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Official URL: https://edoc.unibas.ch/61868/
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Abstract
How systemic metabolic alterations during acute infections impact immune cell function remains poorly understood. We found that acetate accumulates in the serum within hours of systemic bacterial infections and that these increased acetate concentrations are required for optimal memory CD8(+) T cell function in vitro and in vivo. Mechanistically, upon uptake by memory CD8(+) T cells, stress levels of acetate expanded the cellular acetyl-coenzyme A pool via ATP citrate lyase and promoted acetylation of the enzyme GAPDH. This context-dependent post-translational modification enhanced GAPDH activity, catalyzing glycolysis and thus boosting rapid memory CD8(+) T cell responses. Accordingly, in a murine Listeria monocytogenes model, transfer of acetate-augmented memory CD8(+) T cells exerted superior immune control compared to control cells. Our results demonstrate that increased systemic acetate concentrations are functionally integrated by CD8(+) T cells and translate into increased glycolytic and functional capacity. The immune system thus directly relates systemic metabolism with immune alertness.
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Immune Cell Biology (King) 03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Immunobiology (Hess C) 03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Immunodeficiency (Recher) |
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UniBasel Contributors: | Hess, Christoph and King, Carolyn and Recher, Mike |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
ISSN: | 1097-4180 (Electronic)1074-7613 (Linking) |
Note: | Publication type according to Uni Basel Research Database: Journal article |
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Identification Number: |
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Last Modified: | 31 May 2020 21:24 |
Deposited On: | 31 May 2020 21:24 |
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