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

Bart Everts, Eyal Amiel, Stanley Ching Cheng Huang, Amber M. Smith, Chih Hao Chang, Wing Y. Lam, Veronika Redmann, Tori C. Freitas, Julianna Blagih, Gerritje J.W. Van Der Windt, Maxim N. Artyomov, Russell G. Jones, Erika L. Pearce, Edward J. Pearce

Research output: Contribution to journalArticlepeer-review

440 Scopus citations

Abstract

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, IKKε 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.

Original languageEnglish
Pages (from-to)323-332
Number of pages10
JournalNature immunology
Volume15
Issue number4
DOIs
StatePublished - Apr 2014

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