The impact of glucose intermediates, lactate and amino acids on macrophage metabolism and function

Abstract

Macrophages (Mφs) are long-lived innate immune cells present in almost all tissues. In addition to phagocytic properties, Mφs are characterized by their plasticity. They are involved in tissue homeostasis, anti-infectious, pro- and anti-inflammatory responses depending on the needs of the tissue. Mφ functional phenotypes are tightly tied to their metabolic pathways. Glucose-related metabolic pathways including glycolysis, pentose phosphate pathway and glycogen metabolism have been associated with the control of inflammatory response. On the contrary, Krebs cycle activity fueled with glutamine or lactate has been associated with Mφs harboring repair properties. For some metabolites, their fate is directly dependent on Mφ phenotype as exemplified with arginase in murine Mφs: proinflammatory Mφs express nitric oxide synthase synthesizing NO while trophic Mφs express arginase-producing L-ornithine and urea. In this chapter, we propose an overview of the metabolic requirement for Mφs function with an emphasis on the differences between human and murine Mφs.