TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKε supports the anabolic demands of dendritic cell activation

被引：841

作者：

Everts, Bart ^{[1
]}

Amiel, Eyal ^{[2
]}

Huang, Stanley Ching-Cheng ^{[1
]}

Smith, Amber M. ^{[1
]}

Chang, Chih-Hao ^{[1
]}

Lam, Wing Y. ^{[1
]}

Redmann, Veronika ^{[1
]}

Freitas, Tori C. ^{[3
]}

Blagih, Julianna ^{[3
]}

van der Windt, Gerritje J. W. ^{[1
]}

Artyomov, Maxim N. ^{[1
]}

Jones, Russell G. ^{[4
]}

Pearce, Erika L. ^{[1
]}

Pearce, Edward J. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA

[2] Univ Vermont, Dept Med Lab & Radiat Sci, Burlington, VT USA

[3] Trudeau Inst Inc, Saranac Lake, NY USA

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

来源：

NATURE IMMUNOLOGY | 2014年 / 15卷 / 04期

基金：

美国国家卫生研究院;

关键词：

NITRIC-OXIDE; AKT; METABOLISM; MACROPHAGES; MEMORY; ACCUMULATION; INHIBITION; PROTECTION; RECEPTORS; REGULATOR;

D O I：

10.1038/ni.2833

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The ligation of Toll-like receptors (TLRs) leads to rapid activation of dendritic cells (DCs). However, the metabolic requirements that support this process remain poorly defined. We found that DC glycolytic flux increased within minutes of exposure to TLR agonists and that this served an essential role in supporting the de novo synthesis of fatty acids for the expansion of the endoplasmic reticulum and Golgi required for the production and secretion of proteins that are integral to DC activation. Signaling via the kinases TBK1, IKK. and Akt was essential for the TLR-induced increase in glycolysis by promoting the association of the glycolytic enzyme HK-II with mitochondria. In summary, we identified the rapid induction of glycolysis as an integral component of TLR signaling that is essential for the anabolic demands of the activation and function of DCs.

引用

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页码：323 / +

页数：12

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