Diabetes-induced gut microbiota dysbiosis results in impaired alveolar macrophage functions and high vulnerability to infuenza virus infection 2229

Abstract Description The recurring threat of influenza virus (IAV) highlights the risk of respiratory viral infections (RVI). Diabetic patients are more susceptible to RVI. While the increased vulnerability of diabetics to IAV infection is well-recognized, the mechanisms underlying this susceptibility remain largely unknown. We analyzed immune cells and gut microbiota in diabetic and control mice and discovered that reduced levels and compromised function of AM in diabetic mice, which correlated with increased susceptibility to IAV infection. Transplanting AM from diabetic mice to healthy mice increased their proneness to severe IAV infection indicating a central role of AM dysfunction in this consequence of diabetes. The ineffectiveness of diabetic AM to manage IAV associated with impaired mitochondrial function. Pharmacologically inhibiting mitochondrial ROS improved mitochondrial function and mitigated IAV infection in diabetic mice. Lastly, diabetic mice exhibited gut microbiota dysbiosis while microbiota transplant from diabetic to non-diabetic mice impair AM mitochondrial function aggravates their susceptibility to severe IAV infection without affecting their glycemic control. Our findings suggest that diabetes-induced gut microbiota dysbiosis leads to AM dysfunction and heightened IAV susceptibility. Improving AM mitochondrial function, through gut microbiota manipulation, offers potential strategies to mitigate the risk of IAV infection in diabetic individuals. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)