Table III.
A summary of 14 papers selected from 180 Pubmed papers published between 1991 and 2013, on the subject of “outer membrane vesicles (OMVs),” published in international journals that studied, using either in vivo or in vitro models, the direct effects on OMVs on human cells
| Anatomical site | Predominant bacteria (genera) | Studies about OMV interaction with human cells | Ref. |
|---|---|---|---|
| Respiratory tract mucosa |
Corynebacterium
Moraxellaceae Pseudomonas Staphylococcus |
OMVs from Moraxella catarrhalis may bind to lipid raft domains in alveolar epithelial cells and be internalized after interaction with Toll-like receptor 2. These OMVs may also modulate the pro-inflammatory response in pharyngeal epithelial cells. | (701) |
| Pseudomonas aeruginosa (PA) secretes OMVs containing a bacterial virulence factor Cif (PA2934), which inhibits cystic fibrosis transmembrane conductance regulator-mediated chloride secretion and thereby reduces the mucociliary clearance of the pathogen. | (702) | ||
| Cif (PA2934) secreted in OMVs by PA selectively increases the amount of the ubiquitinated transporter associated with antigen processing and its degradation in the proteasome of airway epithelial cells. Cif inhibits MHC class I antigen presentation. | (703) | ||
| Oropharyngeal mucosa |
Aggregatibacter
Haemophilus Lactobacillus Moraxella Neisseria Porphyromonas (a) Staphylococcus Streptococcus |
Porphyromonas gingivalis (PG)a OMVs significantly inhibit the proliferation of cultured gingival fibroblasts and endothelial cells in a dose-dependent manner. Data suggest that PG OMVs contribute to chronic periodontitis. | (704) |
| Moraxella catarrhalis is endocytosed and killed by tonsillar B cells, whereas its OMVs have the potential to interact and activate B cells leading to bacterial rescue. | (705) | ||
| OMVs of PGa cause cell detachment when added to a monolayer of oralsquamous epithelial cells; the effect was inhibited by preincubating OMVs with anti-gingipain antiserum. Hence, PG OMVs may contribute to tissue destruction in periodontal diseases. | (706) | ||
| OMV proteins of Aggregatibacter actinomycetemcomitans are internalized in gingival fibroblasts via a mechanism of OMV fusion with lipid rafts, inducing a cytolethal effect. OMVs deliver cytolethal toxin and additional virulence factors into periodontium. | (707) | ||
| Haemophilus influenza (NTHI) OMVs can bind to pharyngeal epithelial cells, resulting in a time- and temperature-dependent aggregation on the host cell surface, with subsequent internalization and secretion of IL8 and LL-37. | (708) | ||
| Stomach mucosa |
Helicobacter
Lactobacillus Staphylococcus Streptococcus |
Low doses of Helicobacter pylori (HP) OMVs from cag PAI+ toxigenic and cag PAI non-toxigenic strains increase proliferation of gastric epithelial cells. At higher doses, effects were growth arrest, increased toxicity and interleukin-8 (IL-8) production. | (709) |
| Treatment with OMV isolated from a toxigenic HP strain (60190) induces an increased micronuclei formation in gastric epithelial cells. OMV-mediated delivery of VacA to the gastric epithelium may constitute a new mechanism for HP-induced gastric cancer. | (710) | ||
| HP OMVs are equipped with all the molecules required to interact with gastric epithelial cells in a manner not dissimilar from the intact pathogen. | (711) | ||
| HP OMVs are internalized in gastric epithelial cells via various pathways, including clathrin-mediated endocytosis. VacA toxin enhances the association of HP OMVs with the cells and the presence of the toxin may allow vesicles to exploit more than one pathway. | (712) | ||
| Helicobacter suisb OMVs were identified as a possible delivery route of γ-glutamyl transpeptidase to lymphocytes residing in the deeper mucosal layers. | (672) | ||
| Small bowel mucosa |
Bifidobacterium
Clostridium Enterobacterium Lactobacillus Staphylococcus Streptococcus |
Campylobacter jejuni (CJ)b OMVs possess cytotoxic activity and induce a host immune response from intestinal epithelial cells (IECs), which was not reduced by OMV pre-treatment with proteinase K or polymyxin B prior to co-incubation with IECs. Pre-treatment of IECs with methyl-beta-cyclodextrin partially blocks OMV-induced host immune responses, indicating a role for lipid rafts in host cell plasma membranes during interactions with CJ OMVs. | (713) |
| Large bowel mucosa | Bifidobacterium, Clostridium, Enterobacteria, Lactobacillus, Streptococcus, Staphylococcus | No studies | |
| Urethral mucosa | Corynebacterium, Staphylococcus | No studies | |
| Vaginal mucosa | Lactobacillus | No studies | |
| Conjunctival mucosa | Corynebacterium, Pseudomonas, Staphylococci, Streptococcus | No studies | |
| Skin | Staphylococcus, Streptococcus | No studies |
Studies on the OMV stimulation of human peripheral blood cells and studies on the use of OMVs in vaccination were omitted, since we focused here on the physiologically relevant interaction of EVs produced by the bacterial flora with the tissues representing the first “barrier” of the human body.
a
Facultative intracellular pathogen.
b
Pathogenic for Homo sapiens. Investigated cell type is highlighted in bold.