Key Points• Neutrophilic granulocytes stimulated with opsonized particles produce microvesicles (MVs) that are able to impair bacterial growth.• Antibacterial effect correlates with number and size of aggregates between bacteria and MVs and depends on cytoskeletal reorganization of MVs.Cell-derived vesicles represent a recently discovered mechanism for intercellular communication. We investigated their potential role in interaction of microbes with host organisms. We provide evidence that different stimuli induced isolated neutrophilic granulocytes to release microvesicles with different biologic properties. Only opsonized particles initiated the formation of microvesicles that were able to impair bacterial growth. The antibacterial effect of neutrophil-derived microvesicles was independent of production of toxic oxygen metabolites and opsonization or engulfment of the microbes, but depended on  2 integrin function, continuous actin remodeling, and on the glucose supply. Neutrophil-derived microvesicles were detected in the serum of healthy donors, and their number was significantly increased in the serum of bacteremic patients. We propose a new extracellular mechanism to restrict bacterial growth and dissemination.
IntroductionCell-derived vesicles (such as exosomes, ectosomes, microvesicles, shedding microvesicles, and microparticles) represent a recently discovered mechanism for cell-cell communication. [1][2][3] Exosomes are small (50-100 nm) vesicles released from multivesicular bodies. 4 They are involved in antigen presentation [5][6][7] and cell-tocell transfer of receptors 8 or RNA, 9,10 thereby influencing or reprogramming neighboring cells and often promoting tumorigenesis. 8,11 Exosomes also play a role in host defense against microorganisms: tracheobronchial epithelial cells produce exosome-like vesicles with antiviral activity, 12 and macrophage-derived exosomes are able to transfer pathogen-associated molecular patterns of opportunistic intracellular pathogens to uninfected cells. 13 Larger vesicles, called microvesicles (MVs) or microparticles express tissue factor on their surface that is capable of initiating coagulation. 14 Both exosomes and MVs of different cellular origin were detected in various body fluids and selective enrichment was related to specific diseases. [15][16][17][18][19] Neutrophilic granulocytes (PMNs) play a critical role in innate immune mechanisms by engulfing, killing, and degrading various microorganisms. PMNs produce larger vesicles (named by the authors alternatively as ectosomes, microparticles, or MVs) after incubation with various stimuli. [19][20][21][22] Microparticles obtained from PMNs stimulated by chemotactic agents or phorbol esters activated cytokine (IL-6) secretion from endothelial cells 23 and platelets, 24 thereby contributing to the procoagulant effect of leukocytederived microparticles. 25 Chemotactic peptide-induced PMNectosomes increase the secretion of the anti-inflammatory cytokine transforming growth factor  26 and interfere with the maturatio...