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

被引：289

作者：

Balmer, Maria L. ^{[1
]}

Ma, Eric H. ^{[2
,3
]}

Bantug, Glenn R. ^{[1
]}

Grahlert, Jasmin ^{[1
]}

Pfister, Simona ^{[4
]}

Glatter, Timo ^{[5
]}

Jauch, Annaise ^{[6
]}

Dimeloe, Sarah ^{[1
]}

Slack, Emma ^{[7
]}

Dehio, Philippe ^{[1
]}

Krzyzaniak, Magdalena A. ^{[8
]}

King, Carolyn G. ^{[9
]}

Burgener, Anne-Valerie ^{[1
]}

Fischer, Marco ^{[1
]}

Develioglu, Leyla ^{[1
]}

Belle, Reka ^{[1
]}

Recher, Mike ^{[6
]}

Bonilla, Weldy V. ^{[8
]}

Macpherson, Andrew J. ^{[10
]}

Hapfelmeier, Siegfried ^{[4
]}

Jones, Russell G. ^{[2
,3
]}

Hess, Christoph ^{[1
]}

机构：

[1] Univ Basel, Dept Biomed, Immunobiol, CH-4031 Basel, Switzerland

[2] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3A 1A3, Canada

[3] McGill Univ, Dept Physiol, 3655 Drummond St, Montreal, PQ H3G 1Y6, Canada

[4] Univ Bern, Inst Infect Dis, CH-3010 Bern, Switzerland

[5] Univ Basel, Biozentrum, Prote Core Facil, CH-4056 Basel, Switzerland

[6] Univ Basel, Dept Biomed, Immunodeficiency, CH-4031 Basel, Switzerland

[7] Swiss Fed Inst Technol Zurich, Inst Microbiol, CH-8093 Zurich, Switzerland

[8] Univ Basel, Div Expt Virol, Dept Biomed, CH-4009 Basel, Switzerland

[9] Univ Basel, Dept Biomed, Transplantat Immunol, CH-4031 Basel, Switzerland

[10] Univ Bern, Maurice Muller Labs DKF, Univ Klin Viszerale Chirurg & Med, Inselspital, CH-3010 Bern, Switzerland

来源：

IMMUNITY | 2016年 / 44卷 / 06期

基金：

加拿大健康研究院; 欧洲研究理事会; 瑞士国家科学基金会;

关键词：

ACETYL-COA; GUT MICROBIOTA; EFFECTOR FUNCTION; RESPONSES; PHOSPHOTRANSACETYLASE; TRANSCRIPTION; ADAPTATION; ACTIVATION; ANTIGEN; GROWTH;

D O I：

10.1016/j.immuni.2016.03.016

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1312 / 1324

页数：13

共 47 条

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