The role of macrophages in the immune system Essay

Macrophages are an essential component in the orchestration and expression of innate immunity and adaptive immune responses. These cells play a central role in inflammation and host defense. Additionally, cells of the monocyte- macrophage lineage fulfill homeostatic functions beyond defense (150). These functions include tissue repair, wound healing, and regulation of metabolic activity (151). The function of macrophages is tailored to their tissue of residence, an adaptation that is driven by tissue-derived factors and by the physiological environment (150). Depending on the microenvironment, macrophages can acquire distinct functional phenotypes. The concept of macrophage polarization was first described in 1992 with the discovery that IL-4 potently enhances murine macrophage mannose receptor (CD206) activity (152). Since then, two opposite and competing phenotypes, often referred to as classically activated macrophages (M1 macrophages) and alternatively activated macrophages (M2 macrophages), have been defined and identified in several physiological settings (153). Although the classification of macrophages as M1/M2 came after the classification of lymphocytes into Th1 and Th2, the Th1 and Th2-like responses are the results of polarization of macrophages to M1 and M2 states, respectively. Furthermore, M1/M2 polarization is not dependent on T cells, as has been demonstrated in Rag-1 knockout and other immune deficient mice (154).
M1 macrophages are induced by TLR ligands (such as LPS) and IFN-. They express higher levels of CD86 and PD-L1 (155). M1 macrophages are characterized by increased microbicidal activity and produce several proinflammatory mediators, such as inducible nitric oxide synthase, TNF-, IL-1, IL-6, IL-12, and proteolytic enzymes (156). They constitute the first line of defense against pathogens and promote Th1 polarization of CD4+ lymphocytes. On the other hand, M2 macrophages are induced by Th2-type cytokines, such as IL-4 and IL-13. Tregs have also been implicated in the induction of M2 polarization, possibly through IL-10 (157). M2-like cells have been described in different pathological conditions such as infections by intracellular bacteria or virus, allergy, diabetes, and cancer (153,158). They are characterized by the expression of CD163, CD206, arginase 1, FIZZ1 (found in inflammatory zone 1), and CD36. In addition, they secrete anti-inflammatory cytokines, such as TGF-, IL-1 receptor antagonist, and IL-10. M2 macrophages play an essential role in the suppression of Th1 immune responses and the enhancement of tissue remodeling and Th2 response (159). Macrophages with intermediate or overlapping phenotypes have also been reported. For example, adipose tissue macrophages from obese mice have a mixed profile, with upregulation of several M1 and M2 gene transcripts (160).
Kim and Hematti were the first to report that MSCs could polarize macrophages from the classic proinflammatory M1 phenotype, toward the anti-inflammatory M2 phenotype (130). They found that macrophages co-cultured with MSCs consistently showed a high level expression of markers for M2 macrophages. The resulting macrophages produced high levels of IL-10 and low levels of IL-12 and TNF-. Functionally, macrophages co-cultured with MSCs showed a higher level of phagocytic activity (Figure 5). Other studies showed that MSC-mediated polarization of M2 macrophages depends on the secretion of soluble factors, including PGE2, TSG-6, IL-6, IDO, and TGF-1