Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation

被引：968

作者：

Krawczyk, Connie M. ^{[2
]}

Holowka, Thomas ^{[2
]}

Sun, Jie ^{[2
]}

Blagih, Julianna ^{[3
,4
]}

Amiel, Eyal ^{[1
]}

DeBerardinis, Ralph J. ^{[5
]}

Cross, Justin R. ^{[6
]}

Jung, Euihye ^{[2
]}

Thompson, Craig B. ^{[6
,7
,8
]}

Jones, Russell G. ^{[3
,4
]}

Pearce, Edward J. ^{[1
,2
]}

机构：

[1] Trudeau Inst, Saranac Lake, NY 12983 USA

[2] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA

[3] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ, Canada

[4] McGill Univ, Dept Pathol, Montreal, PQ, Canada

[5] Univ Texas SW Med Ctr Dallas, Dept Pediat & Genet, Dallas, TX 75390 USA

[6] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

[7] Univ Penn, Dept Canc Biol, Philadelphia, PA 19104 USA

[8] Univ Penn, Fac Med, Philadelphia, PA 19104 USA

来源：

BLOOD | 2010年 / 115卷 / 23期

基金：

美国国家卫生研究院;

关键词：

ADAPTIVE IMMUNE-RESPONSES; ANTIINFLAMMATORY RESPONSE; GLUCOSE-METABOLISM; PYRUVATE-KINASE; GROWTH; AUTOPHAGY; PATHWAY; PROTEIN; CANCER; ENERGY;

D O I：

10.1182/blood-2009-10-249540

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Dendritic cells (DCs) are key regulators of innate and acquired immunity. The maturation of DCs is directed by signal transduction events downstream of toll-like receptors (TLRs) and other pattern recognition receptors. Here, we demonstrate that, in mouse DCs, TLR agonists stimulate a profound metabolic transition to aerobic glycolysis, similar to the Warburg metabolism displayed by cancer cells. This metabolic switch depends on the phosphatidyl inositol 3'-kinase/Akt pathway, is antagonized by the adenosine monophosphate (AMP)-activated protein kinase (AMPK), and is required for DC maturation. The metabolic switch induced by DC activation is antagonized by the antiinflammatory cytokine interleukin-10. Our data pinpoint TLR-mediated metabolic conversion as essential for DC maturation and function and reveal it as a potential target for intervention in the control of excessive inflammation and inappropriately regulated immune responses. (Blood. 2010;115(23):4742-4749)

引用

页码：4742 / 4749

页数：8

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