Synaptic-like coupling of macrophages to myofibers regulates muscle repair.

Peripheral injury responses essential for muscle repair and nociception require complex interactions of target tissues, immune cells, and primary sensory neurons. Nociceptors and myofibers both react robustly to signals generated from circulating immune cells, which promote repair, growth, and regeneration of muscle while simultaneously modulating peripheral sensitization. Here, we found that macrophages form a synaptic-like contact with myofibers to hasten repair after acute incision injury and to facilitate regeneration after major muscle damage. Transient chemogenetic activation of macrophages enhanced calcium-dependent membrane repair, induced muscle calcium transients in vivo, elicited low-level electrical activity in the muscles, and enhanced myonuclear accretion. Under severe injury, macrophage activation could also modulate pain-like behaviors. This study identifies a novel mechanism by which synaptic-like functions of macrophages impact muscle repair after tissue damage.