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

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

doi:10.1038/ni.2833

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

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Pearce, Erika L.
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pearce, Edward J.
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Everts, B., Amiel, E., Huang, S.-C.-C., Smith, A. M., Chang, C.-H., Lam, W. Y., et al. (2014). TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKɛ supports the anabolic demands of dendritic cell activation. Nature Immunology, 15, 323-332. doi:10.1038/ni.2833.

Cite as: https://hdl.handle.net/21.11116/0000-0006-5432-3

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, 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.