Speaker
Description
In humans, differences in immune response between males and females influence influenza infection outcomes. During the 2009 H1N1 pandemic, Eshima et al., 2011 found that adult females were ~40% more likely to be hospitalized than their male age-matched counterparts. The innate immune response has been implicated as a factor of these sex differences. Together with collaborators at UW Madison, we have completed experiments on male and female mice infected with CA04-H1N1 influenza. These experiments show that female mice have increased viral production at 36 hours post infection and early, excessive innate immune activation characterized by proinflammatory cytokine profiles, and critical differences in macrophage counts. Histopathology shows lesions are present in the alveolar region of female, but not male, mice, indicating influenza virus penetrates more deeply in female lungs. While experimental data identifies key immune components linked to severity, mathematical modeling enables detection of sex-specific mechanistic differences. We developed a mathematical model of influenza infection to identify mechanisms responsible for observed increases in disease severity in female mice. We have identified two models with significant evidence using Bayesian model selection (AICc), where each model has a different parameter subset with individual male and female values. These parameters are sex-specific and each model points to a unique mechanism that could be targeted for regulating severe influenza disease.
