Abstract
Very little is known about the muscle regeneration process that follows myonecrosis induced by C. perfringens, the main agent of gas gangrene. This study revealed that, in a murine model of the infection with a sublethal inoculum of C. perfringens, muscle necrosis occurs concomitantly with significant vascular damage, 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 Ml macrophages, a deficient phagocytic activity, and the prolongation of the permanence of inflammatory cells, lead to deficient muscle regeneration. The expression of TGFβ1 and the consequent accumulation of collagen in the muscle, likely contribute to the 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 poor muscle regenerative activity, and may open new perspectives for the development of novel therapies for patients suffering this disease.
Author contributions
Conceptualized, supervised and obtained funds for the project: MF-D; Conceived and designed experiments: MF-D, AA-G, AMZ-P, CS; Conducted experiments: AMZ-P, MF-D, CS; Analyzed data: MF-D, AA-G, AMZ-P, CS, JMG. Wrote the paper: MF-D, AA-G, AMZ-P; Edited the paper: MF-D, AA-G, AMZ-P, CS, JMG.
Footnotes
↵* alberto.alape{at}ucr.ac.cr
Data Availability statement: All relevant data are within the paper.
Funding: This study was funded by Vicerrectoria de Investigation, Universidad de Costa Rica (Project No 741-B8-135 to MF-D). The funder had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscipt.
Competing interest: The authors have declared that no competing interests exist.