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

细菌源性外膜囊泡 (OMV) 在诱导全身炎症和器官损伤中的作用

• 批准号: 521670042
• 负责人: Professorin Dr. Petra Dersch
• 金额: --
• 依托单位: Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/521670042?language=en
• 关键词: Role; Bacteria; derived; Outer; Membrane

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.

通过血管内皮细胞调节血管通透性和白细胞迁移是全身炎症发病机制中的关键过程。这些过程的失调可能会导致组织水肿形成和细胞介导的器官组织破坏，从而引起广泛的损伤。目前的研究表明，细菌外膜囊泡 (OMV) 在全身炎症中具有巨大重要性，特别是在肺炎和败血症等临床疾病中，这些临床疾病是全世界导致死亡的主要原因之一。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问题。根据初步结果，假设革兰氏阴性菌（例如大肠杆菌和肺炎克雷伯菌）的OMV在感染期间诱导全身炎症、血管内凝血和肺/器官损伤中发挥主要作用。这些知识对于开发控制这些疾病的新策略至关重要，并且对于开发 OMV 作为早期诊断工具的潜力也很重要。该项目将表征不同临床相关菌株（例如大肠杆菌和肺炎克雷伯菌）在体内和体外不同炎症条件下分离的 OMV 的释放和组成。 OMV 在复杂生物系统中的病理生理学作用将在不同的炎症性疾病（例如细菌性肺炎）小鼠体内模型中进行研究。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。