Dante Reyna

In diabetes, poor insulin production or response results in hyperglycemia. Hyperglycemia has been associated with many complications, including an increased susceptibility to skin infections. Among the most common skin infections are those caused by opportunistic fungal pathogens, the most common of which is caused by the dimorphic fungus Candida albicans. Candida Albicans (C.albicans) is a resident member of the normal flora, naturally colonizing the skin, genital, and intestinal mucosa in up to 70% of individuals. In healthy individuals, C.albicans is a resident member of the normal flora in the gastrointestinal tract and mucous membranes. However, endogenous infections from the person’s flora often occur in uncontrolled hyperglycemia. These C.albicans infections present a major public health burden in people with metabolic distress. Despite the high incidence of C. albicans in obese and diabetic individuals, little is known about the process of infection within the diabetic population. Furthermore, a disproportionate incidence rate of C.albicans infections affects African-American and Indigenous populations. In the past, our lab has shown that depletion of macrophages in hyperglycemic mice improved host defense, it is likely that macrophages in diabetic skin are promoting an overwhelming inflammatory response. My project seeks to elucidate the contribution the innate immune system has in C.albicans pathogenesis. This proposal aims to fill gaps in our understanding on chronic hyperglycemia triggers and the unusual inflammatory response during C. albicans infection, leading to tissue destruction, fungal dissemination, and death.