Bacterial extracellular vesicles and their interplay with the immune system

Bacterial extracellular vesicles (bEV) are nanosized (~20–300 nm) membrane vesicles that are spontaneously released by bacteria, although different compounds and stress responses may also induce their liberation. While it was initially thought that they could only be released by gram-negative bacteria, it was later discovered that these vesicles may traverse the thick peptidoglycan layers that surround gram-positive bacteria and be discharged into the extracellular space (Lee et al., 2009). Based on their origin and structure, these vesicles have been given multiple names across the years, with “outer membrane vesicle” used most commonly to refer to vesicles formed from the outer membrane of gram-negative bacteria. In contrast, “membrane vesicle” or “cytoplasmic membrane vesicle” was used to refer to those from gram-positive bacteria. As the heterogeneity of these vesicles is increasingly recognized, the broader appellation “bacterial extracellular vesicle” will be used in this review article to refer to all vesicles of bacterial origin.

bEVs are referred to as the bacterial secretion system type 0, as they represent an additional and distinct route to release or deliver bacterial components compared to other secretion methods (Guerrero-Mandujano, Hernandez-Cortez, Ibarra, & Castro-Escarpulli, 2017). The varied content of bEVs allows them to interact with numerous cell types from all domains of life (Gill, Catchpole, & Forterre, 2019), which, combined with their ability to penetrate mucosal barriers, grants bEVs unique potential as immunomodulatory agents. This review recapitulates the current knowledge of mechanisms that govern bEV biogenesis and their heterogeneity. It describes the most recent discoveries in regard to the interactions between bEVs from both gram-negative and gram-positive bacteria and the mammalian immune system, and the properties of bEVs that have been exploited for therapeutic purposes.

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