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Abstract

Monocytes in humans consist of 3 subsets; CD14+CD16−(classical),CD14+CD16+ (intermediate) and CD14dimCD16+ (non-classical), which exhibitdistinct and heterogeneous responses to activation. During acute inflammationCD14+CD16− monocytes are significantly elevated and migrate to the sites of injuryvia the adhesion cascade. The field of immunometabolism has begun to elucidatethe importance of the engagement of specific metabolic pathways in immune cellfunction. Yet, little is known about monocyte metabolism and the role of metabolismin mediating monocyte activation and adherence to vessels. Accordingly, we aimed todetermine whether manipulating the metabolism of CD14+CD16− monocytes alterstheir ability to become activated and adhere. We discovered that LPS stimulationincreased the rate of glycolysis in human CD14+CD16− monocytes. Inhibition ofglycolysis with 2-deoxy-D-glucose blunted LPS-induced activation and adhesionof monocytes. Mechanistically, we found that increased glycolysis was regulatedby mTOR-induced glucose transporter (GLUT)-1. Furthermore, enhanced glycolysisincreased accumulation of reactive oxygen species (ROS) and activation of p38 MAPK,which lead to activation and adhesion of monocytes. These findings reveal that glycolyticmetabolism is critical for the activation of CD14+CD16− monocytes and contributesto our understanding of the interplay between metabolic substrate preference andimmune cell function.

Item Type:	Article
Authors/Creators:	Lee, MKS and Al-sharea, A and Shihata, WA and Bertuzzo Veiga, C and Cooney, OD and Fleetwood, AJ and Flynn, MC and Claeson, E and Palmer, CS and Henstridge, DC and Hamilton, JA and Murphy, AJ
Keywords:	immunometabolism, mitochondria
Journal or Publication Title:	Frontiers in immunology
Publisher:	Frontiers Research Foundation
ISSN:	1664-3224
DOI / ID Number:	10.3389/fimmu.2019.02054
Copyright Information:	Copyright 2019 Lee, Al-Sharea, Shihata, Bertuzzo Veiga, Cooney, Fleetwood, Flynn, Claeson, Palmer, Lancaster, Henstridge, Hamilton and Murphy. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
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