Estrogen treatment predisposes to severe and persistent vaginal candidiasis in diabetic mice

BACKGROUND: Increased levels of estrogen and diabetes mellitus separately predispose to vaginal candidiasis (VC). However, the compounding effect of estrogen on the severity and persistence of VC in diabetic females is not clear. METHODS: To address this issue, a diabetic mouse model with estrogen-maintained VC was developed and evaluated for vaginal fungal burden (VFB) and immune competence at different time points throughout the study period. RESULTS: Blood glucose levels in estrogen-treated diabetic mice were consistently lower than that in untreated counterparts. Estrogen-treated C. albicans-infected non-diabetic mice experienced persistent episodes of VC as compared with naïve controls (P < 0.01). However, severity and persistence of VC in estrogen-treated C. albicans-infected diabetic mice was significantly greater than that in non-diabetic counterparts (P < 0.05). Mortality rates among estrogen-treated C. albicans-infected diabetic mice were significantly higher (P < 0.05) than that in non-diabetic counterparts. Statistically significant (P < 0.05) and persistent suppression of the delayed hypersensitivity response (DTH) was evident in estrogen-treated C. albicans-infected diabetic and non-diabetic mice as compared with controls. Levels of expression of the inhibitory molecule CD152 on vaginal and splenic T cells isolated from estrogen-treated C. albicans infected mice was significantly higher than that in naive untreated controls (P < 0.01). CONCLUSIONS: These findings suggest that estrogen treatment in diabetic females may protect against the progression of DM on the one hand and predispose to severe and persistent VC on the other. The later outcome could be related to the immunosuppressed status of the host.