Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell migration

• DOI: 10.1038/s41467-018-04804-6
• Publication Date: 2018-06-19T11:23:25Z
• Authors: Hannah Guak; Sara Al Habyan; Eric H. Ma; Haya Aldossary; Maia Al-Masri; So Yoon Won; Thomas Ying; Elizabeth D. Fixman; Russell G. Jones; Luke M. McCaffrey; Connie. M. Krawczyk
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Receptors, CCR7; Science; Q; Cell Differentiation; Dendritic Cells; Article; Oxidative Phosphorylation; Mitochondria; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Cell Movement; Animals; Female; Lymph Nodes; Cell Shape; Glycolysis

AbstractDendritic cells (DCs) are first responders of the innate immune system that integrate signals from external stimuli to direct context-specific immune responses. Current models suggest that an active switch from mitochondrial metabolism to glycolysis accompanies DC activation to support the anabolic requirements of DC function. We show that early glycolytic activation is a common program for both strong and weak stimuli, but that weakly activated DCs lack long-term HIF-1α-dependent glycolytic reprogramming and retain mitochondrial oxidative metabolism. Early induction of glycolysis is associated with activation of AKT, TBK, and mTOR, and sustained activation of these pathways is associated with long-term glycolytic reprogramming. We show that inhibition of glycolysis impaired maintenance of elongated cell shape, DC motility, CCR7 oligomerization, and DC migration to draining lymph nodes. Together, our results indicate that early induction of glycolysis occurs independent of pro-inflammatory phenotype, and that glycolysis supports DC migratory ability regardless of mitochondrial bioenergetics.