PR000066 (Project)

Description:During the 2009 H1N1 influenza pandemic outbreak, obese individuals were reported to be at greater risk for morbidity and mortality from pandemic infection. However, the mechanisms contributing to greater influenza severity in infected obese individuals remain unclear. Given that one in ten individuals is obese, and worldwide influenza outbreaks are a consistent public health burden, garnering a better understanding of the pathways and mechanisms contributing to greater influenza severity in the obese is essential for limiting influenza infection mortality in this at-risk population. Closely paralleling pH1N1 infection outcome in humans, obese mice exhibit increased morbidity and mortality following pH1N1 infection. In mice, obesity impairs the function of natural killer cells, dendritic cells, macrophage, B cells and memory T cells. Further, several analyses of lung antiviral responses revealed that obese mice have greater lung damage, lung immune cell infiltration and impaired lung healing after infection. Nevertheless, it remains unclear how altered immune cell function contributes to greater lung damage and increased infection severity in obese mice. Metabolomics will be used to dissect the metabolic consequences of obesity on the immune response to pH1N1 infection. We will compare metabolic profiles of lung-specific and peripheral samples from uninfected and infected lean and obese mice during early and late phases of influenza immunity.