Reprogramming of Central Carbon Metabolism in Myeloid Cells upon Innate Immune Receptor Stimulation

Laure Perrin-Cocon,Olivier Diaz,Pierre-Olivier Vidalain,Vincent Lotteau,Anne Aublin-Gex

doi:10.3390/immuno1010001

Abstract

Immunometabolism is a relatively new field of research that aims at understanding interconnections between the immune system and cellular metabolism. This is now well-documented for innate immune cells of the myeloid lineage such as macrophages and myeloid dendritic cells (DCs) when they engage their differentiation or activation programs. Several studies have shown that stimulation of DCs or macrophages by the binding of pathogen-associated molecular patterns (PAMPs) to pattern recognition receptors (PRRs) leads to increased glycolytic activity and rewiring of central carbon metabolism. These metabolic modulations are essential to support and settle immunological functions by providing energy and immunoregulatory metabolites. As the understanding of molecular mechanisms progressed, significant differences between cell types and species have also been discovered. Pathways leading to the regulation of central carbon metabolism in macrophages and DCs by PRR signaling and consequences on cellular functions are reviewed here.

Highlights

It is widely accepted that the metabolic status and effector functions of immune cells are intimately connected [1]
In murine bone-marrow-derived dendritic cells (BMDCs) stimulated through TLR4 by LPS, the early increase in glycolysis is controlled by activation of TBK1, IKKε and AKT kinases, favoring mitochondrial translocation of HK2 [9]
In murine macrophages and dendritic cells (DCs) stimulated by LPS, the signaling of mammalian target of rapamycin complex 1, whose activation depends on available nutrients including glucose, is sustained, and HIF-1α is upregulated, increasing glycolysis and triggering inducible nitric oxide synthase (iNOS)

Summary

Introduction

It is widely accepted that the metabolic status and effector functions of immune cells are intimately connected [1]. Main functions include endocytosis and phagocytosis of pathogens, secretion of antimicrobial, inflammatory and immunoregulatory factors, and presentation of antigens to lymphoid cells. Both macrophages and DCs are from the myeloid lineage and express a large panel of pattern recognition receptors (PRRs) such as toll-like receptors (TLRs) and RIG-like receptors (RLRs), allowing the detection of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). When PRRs are engaged by their cognate ligands, macrophages and DCs are activated and undergo in-depth metabolic reprogramming These modulations are required for these cells to fulfill their immunological functions [2,3]. Immuno 2021, 1 and DCs upon activation by PRRs and how this can lead to the production of specific immunomodulatory metabolites by these cells

Glycolysis in Cell Bioenergetics

PRR Stimulation Triggers a Glycolytic Reprogramming of Immune Cells

Mechanisms Controlling Glycolytic Reprogramming in Myeloid Cells

TLR4 signaling the central carbonofmetabolism of macrophages myeloid

TCA Rewiring

Lipid Metabolism

Conclusions and Perspectives