Infection and tissue repair of experimental cutaneous candidiasis in diabetic mice.

Abstract

Diabetic patients seem to be predisposed to cutaneous candidiasis. In this study, we evaluated the interference of diabetic conditions in alloxan-induced diabetic mice in relation to the development of C. albicans infection, density of M1 and M2 macrophages, distribution of collagen type I and III and anti-inflamamatory cytokines involved in tissue repair. The mice were treated with intravenous alloxan, and all animals with blood glucose levels >250 mg dl-1 were inoculate with C. albicans intradermally in the hind paw and were studied for up to 21 days. Control groups without alloxan were used. The fungal burden was evaluated by periodic acid-Schiff (PAS) and by counting the colony forming units. Total population of macrophages were targeted with antibody to F4/80 antigen and M2 macrophages with anti-arginase antibody. Anti-inflammatory cytokines from popliteal lymph nodes were determined by capture ELISA procedures. Picrosirius red staining allowed qunantification of collagen types I and III in the infected skin by using a polarized light microscope.Results/Key findings. Diabetic mice, versus non-diabetic mice, showed a significant lower density of F4/80 and M2 macrophages, higher fungal burden, deficiency in interleukin (IL)-4 production, and delayed IL-13 responses. The later clearance of C. albicans enhanced tissue injury, leading to a decrease in collagen type I. Moreover, collagen type III was increased by interference of IL-13 and transforming growth factor-β cytokines. These findings highlight some important changes in diabetic animal responses to C. albicans infection that may be important to the pathophysiological processes underpinning cutaneous candidiasis in diabetic patients.