Memory CD8(+) T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function.

Balmer, Maria Luisa; Ma, Eric H; Bantug, Glenn R; Grählert, Jasmin; Pfister, Simona; Glatter, Timo; Jauch, Annaïse; Dimeloe, Sarah; Slack, Emma; Dehio, Philippe; Krzyzaniak, Magdalena A; King, Carolyn G; Burgener, Anne-Valérie; Fischer, Marco; Develioglu, Leyla; Belle, Réka; Recher, Mike; Bonilla, Weldy V; Macpherson, Andrew; Hapfelmeier, Siegfried Hektor; ... (2016). Memory CD8(+) T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function. Immunity, 44(6), pp. 1312-1324. Cell Press 10.1016/j.immuni.2016.03.016

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Balmer, Maria Luisa; Pfister, Simona; Macpherson, Andrew and Hapfelmeier, Siegfried Hektor

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1074-7613

Publisher:

Cell Press

Language:

English

Submitter:

Siegfried Hektor Hapfelmeier-Balmer

Date Deposited:

06 Jan 2017 14:43

Last Modified:

06 Mar 2017 13:58

Publisher DOI:

10.1016/j.immuni.2016.03.016

PubMed ID:

27212436

BORIS DOI:

10.7892/boris.91969

URI:

https://boris.unibe.ch/id/eprint/91969

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