Differences in the male and female immune response to Cryptococcus neoformans infections<

Abstract

Abstract Introduction Cryptococcus neoformans (Cn) is responsible for an estimated 220,000 cases of cryptococcus, resulting in more than 181,000 deaths each year worldwide. Prevalence of this disease is skewed between males and females. Numerous studies show differences in Cn infection rates, with males having a higher incidence of disease and death (7:3, m:f). Sexual dimorphism in infections is not uncommon. However, these differences in Cn have not been well elucidated. Our goal is to unravel the complexity of sex-specific, host-pathogen interactions by examining the effect of sex on the immune response to Cn and whether sex hormones contribute to those differences. We hypothesize that males have an increased incidence of disease due, at least in part, to differences in immune response during a Cn infection. Methods Peripheral blood mononuclear cells were isolated from 40 healthy volunteers and infected with Cn. Physiological levels of testosterone and estrogen were added to subsets of all infections. Infected cells were incubated for seven days after which they were harvested and B- and T-cell responses assessed via flow cytometry. Analytes measured include: CD3, CD4, CD8 (T-cell markers), and CD19 (B-cell marker). Serotyping was done on all samples and correlated with immune response. Results Subjects with previous exposure to Cn exhibited an increased CD19 response. Data show lower numbers of all T-cell markers in males during infection. There was no difference in hormonal treatment groups. Discussion The sexual dimorphism seen in Cn infections is commonly observed, but understanding what accounts for these differences is unknown. These results could aid in understanding why males have increased disease in Cn infections.