Abstract

Macrophages are a well recognized player of both innate and adaptive immunity and have emerged as a key regulator of systemicmetabolism, hematopoiesis, vasculogenesis, apoptosis, malignancy, and reproduction. Such pleiotropic roles of macrophages are mirrored by their protean features. Upon environmental. challenges, macrophages redistribute and differentiate in situ and contribute to the multiple disease states by exerting protective and pathogenic effects. The environmental challenges include cytokines, chemokines, lipid mediators, and extrinsic insults, such as food and pathogenic bacteria. In addition, homeostasis and the activation state of macrophages are influenced by various metabolites from a commensal microbe that colonizes epithelial and mucosal surfaces, such as the lungs, intestines, and skin. In this review, we describe macrophage differentiation, polarization, and various functions in chronic disease states, including chronic inflammatory bowel disease, tumorigenesis, metabolism and obesity, and central nervous system demyelinating disorders. Controlling the macrophage dynamics to affect the pathologic states is considered to be an important therapeutic approach for many clinical disorders involving chronic inflammation.