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

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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.