Functional Polarization of Mononuclear Phagocytes

Functional Polarization of Mononuclear Phagocytes Mononuclear phagocyte (MP) encompass bone marrow precursor cells and peripheral blood monocytes that, after a very short time (1–2 days), migrate into the different organs and tissues. Under the influence of the different microenvironments, recently migrated monocytes give rise to a variety of MP subtypes, including mucosal macrophages, dendritic cells, and tissue-associated Langherans cells of skin, perivascular macrophages, Kupffer cells of liver, and brain microglial cells. In addition to their peculiar differentiation phenotypes, tissue macrophages may be activated along 2 main functional pathways. Proinflammatory stimuli result in classically activated macrophages or M1-cells, which participate to the clearance of either infected or transformed cells, however simultaneously contributing to tissue destruction. Conversely, anti-inflammatory signals induce alternatively activated or M2-macrophages that will activate cellular programs, promoting tissue regeneration and wound healing. M1-macrophages are typically induced by microbial products and proinflammatory cytokines, particularly interferon-γ (IFN-γ), and are potent effector cells enabled to kill cells infected by intracellular pathogens, including viruses, and tumor cells; they are also sources of proinflammatory cytokines, such as interleukin (IL)-1β, IL-12, IL-15, IL-18, and tumor necrosis factor-α, thus participating to the induction and maintenance of CD4 T helper cells 1 responses. In addition, M1-cells secrete factors of the Complement cascade and express high levels of major histocompatibility complex class I and class II antigens, thereby enhancing the adaptive immune response to pathogens or tumors. In contrast, IL-4, IL-13, glucocorticoid hormones, IL-10, and antigen-antibody (Ab) complexes, in combination with cell stimulation via toll-like receptor, induce M2 functional polarization of tissue macrophages. This activation state is characterized by poor production of nitric oxide (NO), reduced to absent secretion of proinflammatory cytokines coupled with the enhanced ability to scavenge cellular debris, promotion of neoangiogenesis, tissue remodeling, and repair. M2-polarized macrophages have also shown an increased capacity to eliminate extracellular pathogens, including parasites, and participate in the switch of the adaptive immune response toward CD4 Th2