Leptin treatment alters the response of respiratory epithelial cells to influenza infection

Abstract

Previous work in our laboratory has demonstrated that diet‐induced obese mice have greater mortality and morbidity when infected with influenza virus. Respiratory epithelial cells are the primary target of influenza virus, and these cells act as the first line of defense. Infection of the respiratory epithelium leads to activation of an intracellular signaling cascade resulting in expression of antiviral cytokines. Regulation of this cascade is controlled by a negative feedback mechanism initiated by proteins from the suppressor of cytokine signaling (SOCS) family. Interestingly, leptin signaling also upregulates SOCS protein expression, and overproduction of leptin is a hallmark of obesity. To determine if leptin exposure affects the response to infection of respiratory cells, A549 human alveolar epithelial cells were treated with 0, 10 and 100 ng/mL of recombinant human leptin in culture for 24 hours. Cells were then inoculated with influenza, and samples were collected at various times post infection. Exposure to increased levels of leptin led to an increase in viral titers. In addition, increased leptin levels also resulted in increased IL‐6 and SOCS‐3 expression. Given the public health significance of both influenza infection and obesity, the results of this study suggest that elevated leptin levels found in the obese state may contribute to increased influenza susceptibility.Grant Funding Source: NIH DK56350