Macrophages: Tissue-Resident Determinants of Immunomodulation

Abstract

Macrophages (MΦs) are mononuclear phagocytes that are found in almost every tissue and are generated from myeloid progenitor-derived monocytes, which differentiate to tissue MΦs upon migration from the peripheral circulation to specific tissue environments. MΦs play a dominant role in the clearing of antigenic materials (pathogenic, infectionand tissue trauma, host-derived) by phagocytosis, driving innate immune responses or instruction of adaptive responses. In fact, MΦs exhibit a wide range of functionality which includes phagocytosis, antigen processing and presentation, pathogen killing, inflammation, anti-inflammatory responses, immune suppression, tissue repair, both proand anti-tumour responses and activation/ instruction of other innate and adaptive immune cells. Such a wide array of functionality, which at times appears to be at opposite ends of a spectrum of effector functionality, cannot surely be exhibited by just one type of effector MΦ. Indeed, MΦs exhibit a functional mosaic which is likely to be shaped by many factors that present themselves in the local tissue environment. This functional mosaicism presents as a consequence of a plethora of environmental influences which include activation and differentiation factors as well as a level of preprogramming in the monocyte recruited to the tissue; all of which coming together to result in distinct functional effector phenotypes or MΦ subsets.