Filex Otieno

By Filex Otieno and Cynthia Kyalo

Macrophages are phagocytic cells that reside within body tissues. They can either be derived from circulating monocytes or can arise during the embryonic stage of fetal development. Tissue macrophages are predominantly of embryonic origin. But can result from differentiation of circulating monocytes to become resident macrophages either in pathological or physiological state. Macrophages are classified based on their tissue location and method of activation. Classically activated macrophages are the M1 phenotype while alternatively activated macrophages are M2 phenotype. M1 macrophages are pro-inflammatory since they secrete cytokines that attract inflammatory mediators. They are majorly activated by either interferon-gamma or lipopolysaccharide molecules. M2 macrophages are anti-inflammatory and mediate tissue healing and repair. They are activated by cytokines such as interleukin four, ten, and thirteen. The metabolic profiles of these classes of macrophages are intrinsically different and complex yet intertwined. M1 macrophages depend on aerobic glycolysis for energy production while M2 macrophages rely on aerobic fatty acid oxidation pathways. These metabolic pathways optimize macrophage functioning. Regulation of both activation and metabolism depends on transcriptional factors such as STAT 1 and 6, and IRF. Defects in these pathways lead to development of disorders related to macrophage activation and metabolism.

Part of the book: Basic and Clinical Aspects of Interferon Gamma

By Filex Otieno

Macrophages are immune cells functioning primarily as antigen-presenting cells. They are professional phagocytes and patrol tissues within the body contributing to immunological surveillance. The majority of circulating macrophages and to some extend tissue-resident macrophages differentiate from monocytes. A few of resident macrophages do however originate from embryo during fetal development and remain capable of self-renewal even in adulthood. Macrophages are highly plastic seeing that they play a dual function in inflammatory conditions: either pro-inflammatory or anti-inflammatory. Depending on state of the body, whether disease, healing or homeostatic state, macrophages can be polarized to either one of two phenotypes-M1 macrophages or M2 macrophages. The former phenotype is associated with pro-inflammatory processes, while the latter mediates anti-inflammatory process. Metabolic process and intermediate substrates influence macrophage activation, polarization and functioning within the body. Moreover, within macrophages themselves, the metabolic pathways activated also influences their polarization. As such inflammatory conditions from either infectious agents or metabolic diseases are a major drive for macrophage activation that determines disease severity and prognosis seemingly because macrophages also activate other immune cells. This interplay between immune system and metabolism is of interest especially in development newer treatment strategies for metabolic diseases and infectious agents.

Part of the book: Phagocytosis