Energy metabolic pathways control the fate and function of myeloid immune cells

Abstract

The past decade has seen a significant interest in investigating the intracellular metabolism of cells of the immune system. This has increased the realization that immune cells endure metabolic reprogramming upon responding to pathogen-derived or inflammatory signals. More importantly, not only does this metabolic switch provide for the bioenergetic and biosynthetic demands but also it, in a highly specific manner, determines the cellular fate and function. In this review, we discuss the metabolic aspects that regulate the differentiation and function of myeloid cells, pivotal for both innate and adaptive immunity. The manipulation of these pathways can alter the function of these cells and therefore, could provide novel therapeutic approaches in cancer and other chronic inflammatory conditions.

Keywords: MDSC; dendritic cell; macrophage; neutrophil.

Figure 1.. An outline of the primary energy metabolic pathways.

Cells produce ATP, the currency of cellular energy, using 3 main interconnected metabolic pathways: glycolysis, the TCA cycle, and OXPHOS. Three other pertinent biochemical pathways—the PPP, glutaminolysis, and FAO—are also depicted.

Figure 2.. Intracellular metabolism regulates myeloid cells.

Myeloid cells of the immune system rely on distinct energy metabolic pathways to support their survival and functions. The metabolic profiles and the molecular mechanisms in cell types, such as tolerogenic DCs and MDSCs, and in the subtypes of myeloid cells remain to be fully determined.