Gas gangrene or clostridial myonecrosis is usually caused by Clostridium perfringens and may occur spontaneously in association with diabetes mellitus, peripheral vascular disease, or some malignancies, but more often after contamination of a deep surgical or traumatic lesion. If not controlled, clostridial myonecrosis results in multiorgan failure, shock and death, but very little is known about the muscle regeneration process that follows myonecrosis when the infection is controlled. In this study we characterized the muscle regeneration process after myonecrosis caused in a murine experimental infection with a sublethal inoculum of C. perfringens vegetative cells. The results show that myonecrosis occurs concomitantly with significant vascular injury, which limits the migration of inflammatory cells. A significant increase in cytokines that promote inflammation explains the presence of inflammatory infiltrate; however, an impaired IFNγ expression, a reduced number of M1 macrophages, a deficient phagocytic activity, and the prolongation of the permanence of inflammatory cells, lead to deficient muscle regeneration. The expression of TGFβ1 agrees with the consequent accumulation of collagen in the muscle, i.e. fibrosis observed 30 days after infection. These results provide new information on the pathogenesis of gas gangrene caused by C. perfringens, shed light on the basis of the deficient muscle regenerative activity, and may open new perspectives for the development of novel therapies for patients suffering from this disease.
