The Role of Bacteria-derived Outer-Membrane-Vesicles (OMVs) in the Induction of Systemic Inflammation and Organ Damage

通过血管内皮细胞调节血管通透性和白细胞迁移是全身性炎症性疾病发病机制中的关键过程。这些过程的失调可能通过造成组织水肿形成和细胞介导的器官组织破坏而诱导广泛的损伤。目前的研究表明，细菌外膜囊泡（OMV）在全身性炎症，特别是在肺炎和败血症，临床疾病，这是世界范围内的死亡率的主要原因之一的巨大的重要性。为了研究OMV在全身炎症过程中与血管内皮和免疫细胞相互作用期间作为生物标志物和治疗靶点的巨大潜力，该项目将通过实验室研究和临床观察试验来解决这些新方面。根据初步研究结果，我们推测革兰氏阴性菌（如大肠杆菌）的OMV可能与革兰氏阴性菌（如大肠杆菌）的OMV有关。埃希菌和肺炎杆菌）在感染期间诱导全身性炎症、血管内凝血和肺/器官损伤中起主要作用。这些知识对于开发控制这些疾病的新策略至关重要，对于开发OMV作为早期诊断工具的潜力也很重要。该项目将表征由不同临床相关细菌菌株分离的OMV的释放和组成，例如，E.埃希菌和肺炎，在体内和体外不同的炎症条件下。OMV在复杂生物系统中的病理生理学作用将在不同的炎性疾病的鼠体内模型中进行研究，例如，细菌性肺炎这也将得到最先进的活体成像技术的补充，例如，肺活体显微镜检查

The regulation of vascular permeability and leukocyte transmigration through vascular endothelial cells is a crucial process in the pathogenesis of systemic inflammatory conditions. Dysregulation of these processes may induce extensive damage by inflicting tissue oedema formation and cell-mediated destruction of organ tissue. Current research has shown the tremendous importance of bacterial outer membrane vesicles (OMVs) in systemic inflammation, particularly in pneumonia and sepsis, clinical maladies which are among the leading causes of mortality world-wide. To investigate the tremendous potential of OMVs as a biomarker and therapeutic target during their interaction with the vascular endothelium and immune cells during systemic inflammation, this project will address these novel aspects by laboratory investigations and clinical observational trials. Based on preliminary results, the hypothesis ist that OMVs of Gram-negative bacteria (such as E. coli and K. pneumoniae) play a major role in the induction of systemic inflammation, intravascular coagulation, and lung/organ damage during the infection. This knowledge will be vital for the development of novel strategies to control these diseases and important to exploit the potential of OMVs as a tool for early-stage diagnostics. This project will characterize the release and composition of OMVs isolated by different clinically relevant bacterial strains, e.g., E. coli and K. pneumoniae, under different inflammatory conditions in vivo and in vitro. The pathophysiological role of OMVs in complex biological systems will be investigated in different murine in vivo models of inflammatory diseases, e.g., bacterial pneumonia. This will also be complemented by state-of-the-art intravital imaging techniques, e.g., lung intravital microscopy.