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Nat Immunol. 2014 Apr;15(4):323-32. doi: 10.1038/ni.2833. Epub 2014 Feb 23.

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

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Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Medical Laboratory and Radiation Sciences, University of Vermont, Burlington, Vermont, USA.
Trudeau Institute, Saranac Lake, New York, USA.
Department of Physiology, McGill University, Montreal, Quebec, Canada.


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, IKKɛ 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.

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