Influence of diabetes mellitus on antibacterial immunity in the lung

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Lower respiratory tract infections represent the fifth leading cause of death worldwide. In the coming years, pneumonia-associated morbidity and mortality may continue to rise as the number of individuals with risk factors for pneumonia, such as diabetes mellitus (among others) growths in many parts of the world. However, the mechanism underlying the enhanced susceptibility of diabetic patients to pneumonia is incompletely understood. Our preliminary results from two different diabetes animal models indicate that diabetes increases susceptibility to Streptococcus pneumoniae and Legionella pneumophila infections and that neutrophil recruitment and IFN and IL-6 production are severely impaired in these animals. Preliminary single cell RNA-seq data further suggest a dysregulated activation status of macrophages. The aim of the proposed project is to further characterize the impact of diabetes on the antibacterial immune defense and metabolism of respiratory immune cells. A better understanding of these mechanisms has the potential to enable more targeted prophylactic and/or therapeutic strategies to protect individuals with diabetic mellitus from pneumonia.