1. The prevalence of obesity has risen dramatically during the past 40 years leading to dramatic increases in chronic diseases associated with a chronic state of low grade inflammation. While obesity is a well recognized risk factor for diabetes and cardiometabolic disease, its role in infectious disease is poorly understood. During the recent COVID-19 pandemic, individuals with obesity and diabetes exhibited a greater severity of illness (higher death rate, greater need for ventilatory support, increased ICU admissions, etc) from SARS-CoV2. Metabolic alterations that occur with obesity disrupt innate immune responses to pathogens in the lung. We are currently exploring the mechanisms by which obesity and diabetes alter metabolism and suppress bactericidal functions of alveolar macrophages and neutrophils during the course of bacterial pneumonia.

2. Leptin is best known for its role in regulating appetite and satiety. We have demonstrated that it plays an essential role in the host defense against bacterial pneumonia by activating distinct intracellular signaling pathways leading to enhanced innate immune responses in alveolar macrophages. Leptin receptor mutations have been identified in humans that contribute to impaired host defense against infections of the gut. Whether similar leptin receptor mutations play a role in susceptibility to pulmonary infections remains to be evaluated.