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

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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Everts B,Amiel E,Huang SC,Smith AM,Chang CH,Lam WY,Redmann V,Freitas TC,Blagih J,van der Windt GJ,Artyomov MN,Jones RG,Pearce EL,Pearce EJ

doi

10.1038/ni.2833

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

323-32

issue

4

eissn

1529-2908

issn

1529-2916

pii

ni.2833

journal_volume

15

pub_type

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