Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell migration

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

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-04804-6

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