REVIEW Bacterial outer membrane vesicles in disease and preventive medicine Can M. Ünal & Viveka Schaar & Kristian Riesbeck Received: 17 November 2010 / Accepted: 18 November 2010 / Published online: 12 December 2010 # Springer-Verlag 2010 Abstract Gram-negative bacteria have the ability to pro- duce outer membrane-derived vesicles (OMVs) that are released into the extracellular milieu. Even though this intriguing phenomenon is well-known since many years, various aspects of bacterial OMVs are not fully described and are still in the process of being characterized in detail. One major reason for this is that depending on the bacterial species and its respective ecological niche, OMVs exhibit an enormous functional diversity. Research of the past years has clearly shown that OMVs of many pathogenic bacteria contribute to the virulence potential by enriching virulence factors and delivering them over long distances, supersed- ing direct bacterial contact with their host. The subsequent interaction of OMVs with the host can occur at different levels regarding the type of immune response or the target cell type and may lead to different outcomes ranging from non-immunogenic activation or a pro-inflammatory re- sponse to cytotoxicity. In contrast to being virulence factors, OMVs are used for vaccination purposes in the combat against bacterial pathogens, and recent research thus is focused on to indirectly aim these versatile bacterial weapons against themselves. Keywords Cytotoxicity . Immunomodulatory . Outer membrane vesicles . Pro-inflammatory response . Vaccine Abbreviations IL Interleukin LPS Lipopolysaccharide MHC Major histocompatibility complex OMV(s) Outer membrane vesicle(s) TIII or TIVSS Type III or IV secretion system TNF-α Tumor necrosis factor-α COPD Chronic obstructive pulmonary disease MCP-1 Macrophage chemoattractant protein-1 IFN-γ Interferon-γ Introduction Bacterial outer membrane vesicles (OMVs) are spherical, bilayered, membranous structures released from the surfa- ces of Gram-negative bacteria [1]. Their first description dates back more than 40 years, when Bishop et al. analyzed the culture supernatants of lysine-requiring Escherichia coli mutants [2]. The scientists were perplexed to find that these mutants under lysine-limiting conditions produced an excess of material they at that time called “extracellular lipoglycopeptide.” Further biochemical and ultrastructural studies revealed that this material was in its composition and appearance similar to the bacterial outer membrane and that the OMVs, or blebs, were produced under common laboratory culture conditions [3–6]. It has later been shown that these vesicles are not products of cell lysis but that they are generated during logarithmic cell growth as well as in stationary phase (Fig. 1). OMVs are sized between 50 and 250 nm in diameter and contain componens of the outer membrane of the bacteria, like lipopolysaccharide (LPS), lipids, adhesins, invasins, toxins, other virulence factors, and sometimes even bacterial DNA. They are associated This article is published as part of the Special Issue on “Small vesicles as immune modulators.” C. M. Ünal : V. Schaar : K. Riesbeck (*) Medical Microbiology, Department of Laboratory Medicine Malmö, Skåne University Hospital, Lund University, 205 02 Malmö, Sweden e-mail: Kristian.Riesbeck@med.lu.se Semin Immunopathol (2011) 33:395–408 DOI 10.1007/s00281-010-0231-y