Sex-specific effects of obestity on Influenza A virus infection and immunity

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Project Summary Obesity is an important comorbidity for worse outcomes from infectious diseases and following vaccination. In humans and mouse models, obesity is associated with severe outcomes from influenza A virus (IAV) infection and inferior protection after influenza vaccination. In non-obese humans and mouse models, we have shown that biological sex plays significant role on IAV pathogenesis and immune responses, mediated by differences in sex steroid hormones and sex chromosomes. However, at present we do not know anything regarding how biological sex modifies the outcomes of IAV infection and immunity in obese population. Obese males and females differ with each other in terms of adiposity, adipokines availability, and inflammatory cells and cytokine concentrations. Therefore, we hypothesize that obesity alters the outcomes of IAV infection and vaccine-induced immunity and protection in a sex-specific manner. Using a mouse model of obesity, in aim 1, we will study sex differences during IAV pathogenesis while aim 2 will experiment sex-specific differences in IAV-vaccine induced immunity and protection. Associations of adipokines, inflammatory cells and cytokines, B and T-cell responses, and sex steroid hormones with IAV pathogenesis and immune responses will be explored among obese and non-obese male and female mice. Thus, this study will fill the critical gap existing in our understanding of interaction between biological sex and obesity during IAV infection and immunity. This will open new avenues to optimize influenza therapeutics and vaccines with better protective efficacies for the obese population.