Macrophage plasticity in skeletal muscle repair

Abstract

Macrophages are one of the first barriers of host defence against pathogens. Beyond their role in innate immunity, macrophages play increasingly defined roles in orchestrating the healing of various injured tissues. Perturbations of macrophage function and/or activation may result in impaired regeneration and fibrosis deposition as described in several chronic pathological diseases. Heterogeneity and plasticity have been demonstrated to be hallmarks of macrophages. In response to environmental cues they display a proinflammatory (M1) or an alternative anti-inflammatory (M2) phenotype. A lot of evidence demonstrated that after acute injury M1 macrophages infiltrate early to promote the clearance of necrotic debris, whereas M2 macrophages appear later to sustain tissue healing. Whether the sequential presence of two different macrophage populations results from a dynamic shift in macrophage polarization or from the recruitment of new circulating monocytes is a subject of ongoing debate. In this paper, we discuss the current available information about the role that different phenotypes of macrophages plays after injury and during the remodelling phase in different tissue types, with particular attention to the skeletal muscle.

Figure 1

Macrophages in acute and chronic muscle damage. The innate immune system through M1 macrophages activates an inflammatory response: secretion of cytokines triggers the clearance of the tissue from the debris and the activation of stem cells. Phagocytosis of apoptotic and necrotic cells induces an M1 to M2 macrophage transition (I). M2 polarized macrophages originate from resident macrophages (II) or can be recruited from circulating monocyte (III). This is a regenerative stage during which stem cells differentiate and the damage is resolved. In chronic diseases several rounds of damage and repair occur: both M1 and M2 polarized macrophages coexist in the tissue, recruited from monocytes. This persistent inflammation leads to fibrosis, fat deposition, and exhaustion of the stem cell pool.