Journal Article

Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell migration

Aldossary, Haya, Won, So Yoon, McCaffrey, Luke M., Ma, Eric H., Guak, Hannah, Ying, Thomas, Al Habyan, Sara, Al-Masri, Maia, Jones, Russell G., Fixman, Elizabeth D., Krawczyk, Connie. M.

2018

Overview

Dendritic 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. The activation of dendritic cells (DC) is associated with a metabolic switch from oxidative to glycolytic metabolism. Here, the authors show that both strong and weak stimuli cause an immediate increase in glycolysis, but only strong stimuli induce long-term glycolytic reprogramming.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/106 / 13/31 / 13/95 / 14/63 / 38/88 / 631/250/2504/133 / 631/45/320 / 631/80/84 / AKT protein / Animals / Bioenergetics / CCR7 protein / Cell activation / Cell adhesion & migration / Cell Differentiation / Cell migration / Cell Movement - immunology / Cell Shape - physiology / Cell size / Dendritic cells / Dendritic Cells - immunology / Dendritic Cells - physiology / Drainage / Elongation / Emergency medical services / External stimuli / Female / First responders / Glycolysis / Glycolysis - physiology / Humanities and Social Sciences / Immune response / Immune system / Inflammation / Innate immunity / Lymph nodes / Lymph Nodes - cytology / Metabolism / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Mitochondria / Mitochondria - metabolism / multidisciplinary / Oligomerization / Oxidative metabolism / Oxidative Phosphorylation / Phenotypes / Receptors, CCR7 - metabolism / Science / Science (multidisciplinary) / Stimuli / TOR protein