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

Gram-negative bacterial strains are common causes of both severe community- and hospital-acquired pneumonia and sepsis. The pathophysiological changes that occur during the infection are characterized by the secretion of a myriad of inflammatory mediators, and the recruitment and activation of innate immune cells to eliminate the pathogen. Insufficient combatting of these invading pathogens triggers cell apoptosis, causing tissue damage and loss of barrier function, allowing leakage of the bacteria into the blood circulation. Unhindered dissemination of bacteria frequently induces an overshooting, aggressive immune response which evokes systemic inflammation, organ damage, and ultimately organ failure, such as acute kidney injury or acute respiratory distress syndrome (ARDS). ARDS patients show characteristic features including increased pro-inflammatory cytokine levels, neutrophil infiltration into the lung, increased permeability, and lung edema formation, and worsened pulmonary gas exchange. Over the past years, it became evident, that diffusible outer membrane vesicles (OMVs), released by Gram-negative bacteria during infection, have a very strong impact on host inflammatory responses and intravascular coagulation, and play a critical role in the pathogenesis, dissemination, and disease progression. Nonetheless, mechanisms underlying the contribution of these vesicles to the propagation of inflammatory processes are so far insufficiently understood.