Macrophage plasticity and the role of inflammation in skeletal muscle repair

Effective repair of damaged tissues and organs requires the coordinated action of several cell types, including infiltrating inflammatory cells and resident cells. Recent findings have uncovered a central role for macrophages in the repair of skeletal muscle after acute damage. If damage persists, as in skeletal muscle pathologies such as Duchenne muscular dystrophy (DMD), macrophage infiltration perpetuates and leads to progressive fibrosis, thus exacerbating disease severity. Here we discuss how dynamic changes in macrophage populations and activation states in the damaged muscle tissue contribute to its efficient regeneration. We describe how ordered changes in macrophage polarization, from M1 to M2 subtypes, can differently affect muscle stem cell (satellite cell) functions. Finally, we also highlight some of the new mechanisms underlying macrophage plasticity and briefly discuss the emerging implications of lymphocytes and other inflammatory cell types in normal versus pathological muscle repair.Funding from MICINN (SAF2009-09782, FIS-PS09/01267, SAF2012-38547, PLE2009-0124, and CIBERNED), AFM, Fundación Marató-TV3, MDA, EU-FP7 (Myoage, Optistem, and Endostem). Y. Kharraz was supported by a postdoctoral fellowship from AF