Biologic Mechanisms of Macrophage Phenotypes Responding to Infection and the Novel Therapies to Moderate Inflammation

Abstract

Pro-inflammatory and anti-inflammatory types are the main phenotypes of the macrophage, which are commonly notified as M1 and M2, respectively. The alteration of macrophage phenotypes and the progression of inflammation are intimately associated; both phenotypes usually coexist throughout the whole inflammation stage, involving the transduction of intracellular signals and the secretion of extracellular cytokines. This paper aims to address the interaction of macrophages and surrounding cells and tissues with inflammation-related diseases and clarify the crosstalk of signal pathways relevant to the phenotypic metamorphosis of macrophages. On these bases, some novel therapeutic methods are proposed for regulating inflammation through monitoring the transition of macrophage phenotypes so as to prevent the negative effects of antibiotic drugs utilized in the long term in the clinic. This information will be quite beneficial for the diagnosis and treatment of inflammation-related diseases like pneumonia and other disorders involving macrophages.

Keywords: biologic mechanism; cellular signal; inflammation; macrophage phenotype.

Figure 1

The schematic diagram of the immune system in pneumonia. It exhibits the procession of lung deterioration and macrophage recruitment. As pneumonia is a complex inflammatory response, the local inflammation will have a detrimental effect on the entire body if the immune system is not able to handle it properly.

Figure 2

Differentiation of macrophage phenotypes. In order to maintain body health, the macrophage population must be normal and appropriate. As explained in this figure, maturation and differentiation of macrophages are closely associated with the function of the immune system.

Figure 3

The pro-inflammatory signaling pathways activated by macrophages mainly include NF-Kappa B, Jak/Stat, IL-6 receptor family, and the Toll-like receptor signal pathway. The activation of these pathways has been strongly associated with the transformation of pro-inflammatory macrophages. The key protein molecules in these pathways are widely studied in the progression of inflammatory transformation.

Figure 4

Signaling pathways that promote the shift of macrophages to an anti-inflammatory phenotype include but are not limited to TGF-β (A), IL-10/mTOR (B), and the Arginine-polyamines-hypusine pathway (C). These pathways are closely associated with T^reg and B^reg cells and thus are used to diagnose the inflammatory process and disease healing.

Figure 5

The function of macrophage phenotypic differentiation and the crosstalk of signaling pathways in wound repair. Inflammatory signals within the immune system, as well as metabolic imbalance, are the factors that support macrophage phenotypic alteration. Despite the fact that rapid macrophage recruitment and activation are capable of fending off the exterior pathogenic organisms, excessive macrophages will worsen tissue if pro-inflammatory macrophages are not quickly reined or changed into repair macrophages. Therefore, the recruitment and polarization of monocytes and macrophages must be strictly regulated during all kinds of tissue injury.