LOW-DOSE STREPTOZOTOCIN-INDUCED DIABETES IN MICE .1. COURSE OF CANDIDA-ALBICANS INFECTION

Diabetic patients are highly susceptible to microbial and fungal infections. To better understand the immune mechanisms underlying the diabetic host-parasite relationship, we studied the course of systemic infection with Candida albicans in mice with low-dose streptozotocin-induced diabetes. For this purpose, we used a low-pathogenic strain of C. albicans, PCA-2, which causes a chronic infection in the intact host. Injection of PCA-2 cells into diabetic mice caused a lethal acute infection. The levels of interferon-γ (IFN-γ,) determined in sera and splenocyte culture supernatants from diabetic mice were significantly higher than those in control mice. Moreover, splenic macrophages from diabetic mice were functionally activated relative to normal macrophages, as evaluated by significantly augmented C. albicans killing in vitro. However, when diabetic mice were infected with PCA-2, IFN-γ levels dropped dramatically to undetectable levels during the first week of infection and there was a marked decrease in macrophage activation. These data suggest that the levels of IFN-γ production early in infection might have a crucial role in generating the susceptibility of diabetic mice to infection. © 1993 Academic Press. All rights reserved.