Macrophage Polarity and Disease Control

Abstract

Macrophages are present in most human tissues and have very diverse functions. Activated macrophages are usually divided into two phenotypes, M1 macrophages and M2 macrophages, which are altered by various factors such as microorganisms, tissue microenvironment, and cytokine signals. Macrophage polarity is very important for infections, inflammatory diseases, and malignancies; its management can be key in the prevention and treatment of diseases. In this review, we assess the current state of knowledge on macrophage polarity and report on its prospects as a therapeutic target.

Keywords: M1; M2; autoimmune diseases; cell-cell interaction; microenvironment; monocytes; tumor-associated macrophages.

Figure 1

M1 macrophages are induced by IFN-γ and LPS, whereas M2 macrophages are induced by IL-4 and IL-10. M1 macrophages exert pro-inflammatory, anti-infectious, and antitumor immunity; these are responsible for inflammatory and autoimmune diseases. M2 macrophages exert anti-inflammatory effects and tissue repair but often promote tumor progression. IFN, interferon; TNF, tumor necrosis factor; LPS, lipopolysaccharide; HMGB1, high mobility group box-1 protein; IL, interleukin; GC, guanylate cyclase; AMP, adenosine monophosphate; CD, cluster of differentiation; MHC, major histocompatibility complex; NOS, nitric oxide synthase; IRF, interferon regulatory factor; STAT, signal transducer and activator of transcription; CXCR, CXC chemokine receptor; ARG, arginase; CXCL, CXC chemokine ligand; TGF, transforming growth factor; CSF-1, colony-stimulating factor-1; VEGF, vascular endothelial growth factor; CCL, CC chemokine ligand.

Figure 2

Positive and negative roles of macrophages. Macrophages exert antitumor effects but can act to promote tumor progression. Macrophages exert antimicrobial effects but can be targets of viruses and cause cytokine storms. Macrophages are responsible for tissue repair and metabolic control but can also cause tissue destruction and metabolic disturbances due to inflammation. IFN, interferon; IL, interleukin; ROS, reactive oxygen species; NO, nitric oxide; VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor; COX, cyclooxygenase; MMPs, matrix metalloprotease; TNF, tumor necrosis factor; ARG, arginase; CCR, CC chemokine receptor; CXCR, CXC chemokine receptor; LDL, low-density lipoprotein.