Differential infection tolerance mediates sex-biased illness severity in sepsis

Sepsis impacts males and females differently. Males have higher incidence, illness severity and mortality in sepsis than females. In this study, we use mouse models of fecal-induced peritonitis (FIP) to study sex disparities in sepsis. Male mice show higher illness severity, physiological derangement and end-organ dysfunction compared to females. Sex-biased outcome was driven by gonadal sex but not chromosome-linked gene effects. The results of this study indicate that male-biased sepsis severity is driven by impaired infection tolerance in males due to sex-biased mechanisms of mitochondrial function. We did not find differences in infection resistance or canonical immune/inflammatory pathways between males and female mice. Here we performed RNA-sequencing on mouse liver hepatocytes of uninfected and septic males and females.