Influence of diabetes mellitus on antibacterial immunity in the lung

下呼吸道感染是全球第五大死亡原因。在未来几年中，肺炎相关的发病率和死亡率可能会继续上升，因为在世界许多地区，具有肺炎风险因素（如糖尿病等）的个体数量会增加。然而，糖尿病患者对肺炎易感性增强的机制尚不完全清楚。我们从两种不同的糖尿病动物模型的初步结果表明，糖尿病增加肺炎链球菌和嗜肺军团菌感染的易感性和中性粒细胞的招聘和IFN和IL-6的生产严重受损，在这些动物。初步的单细胞RNA-seq数据进一步表明巨噬细胞的激活状态失调。该项目的目的是进一步表征糖尿病对呼吸道免疫细胞的抗菌免疫防御和代谢的影响。更好地了解这些机制有可能使更多的针对性的预防和/或治疗策略，以保护糖尿病患者免受肺炎。

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.