Dataset Information

Comparative study of pathogenic and non-pathogenic Escherichia coli outer membrane vesicles and prediction of host-interactions with TLR signaling pathways.

ABSTRACT:

Objective

The intestine is the major defensive barrier in the body by having more than 60% of the immune cells in the intestinal mucosa. The aim of this study was to evaluate the Toll like receptor (TLR) signaling pathways and immune response profiles, against outer membrane vesicles (OMVs) in pathogenic and non-pathogenic strains of Escherichia coli.

Results

Our results demonstrated that despite inducing inflammatory and regulatory responses to OMVs released by both strains, there is a remarkable difference in the nature and severity of these responses between the two strains. Following the production and release of OMV by the pathogenic strain, the expressions of the pro-inflammatory cytokines were significantly elevated, in comparison to the non-pathogenic strains. Eventually, our findings suggest that OMV released by the pathogen strain might be colonized, causing inflammation, eliminating the tight junctions of epithelial cells and damaging underlying cells, without the presence of IL-17 at the inflammation site. This could have happened to prevent the development of more severe inflammation, which could lead to the inhibition of colonization. The production of IL-10 is also preventing such inflammations. On the other hand, OMV released by non-pathogenic E. coli appears to influence intestinal homeostasis by causing more anti-inflammatory responses and mild inflammation.

SUBMITTER: Behrouzi A

PROVIDER: S-EPMC6071399 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

Comparative study of pathogenic and non-pathogenic Escherichia coli outer membrane vesicles and prediction of host-interactions with TLR signaling pathways.

Behrouzi Ava A Vaziri Farzam F Riazi Rad Farhad F Amanzadeh Amir A Fateh Abolfazl A Moshiri Arfa A Khatami Shohreh S Siadat Seyed Davar SD

BMC research notes 20180801 1

<h4>Objective</h4>The intestine is the major defensive barrier in the body by having more than 60% of the immune cells in the intestinal mucosa. The aim of this study was to evaluate the Toll like receptor (TLR) signaling pathways and immune response profiles, against outer membrane vesicles (OMVs) in pathogenic and non-pathogenic strains of Escherichia coli.<h4>Results</h4>Our results demonstrated that despite inducing inflammatory and regulatory responses to OMVs released by both strains, ther ...[more]

PMID: 30068381

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Project description:BackgroundThe well-known fact that avian pathogenic Escherichia coli (APEC) is harder to prevent due to its numerous serogroups has promoted the development of biological immunostimulatory materials as new vaccine candidates in poultry farms. Bacterial outer membrane vesicles (OMVs), known as spherical nanovesicles enriched with various immunostimulants, are naturally secreted by Gram-negative bacteria, and have gained much attention for developing effective vaccine candidates. Recent report has demonstrated that OMVs of APEC O78 can induce protective immunity in chickens. Here, a novel multi-serogroup OMVs (MOMVs) vaccine was developed to achieve cross-protection against APEC infection in broiler chickens.ResultsIn this study, OMVs produced by three APEC strains were isolated, purified and prepared into MOMVs by mixing these three OMVs. By using SDS-PAGE and LC-MS/MS, 159 proteins were identified in MOMVs and the subcellular location and biological functions of 20 most abundant proteins were analyzed. The immunogenicity of MOMVs was evaluated, and the results showed that MOMVs could elicit innate immune responses, including internalization by chicken macrophage and production of immunomodulatory cytokines. Vaccination with MOMVs induced specific broad-spectrum antibodies as well as Th1 and Th17 immune responses. The animal experiment has confirmed that immunization with an appropriate dose of MOMVs could not cause any adverse effect and was able to reduce bacteria loads and pro-inflammatory cytokines production, thus providing effective cross-protection against lethal infections induced by multi-serogroup APEC strains in chickens. Further experiments indicated that, although vesicular proteins were able to induce stronger protective efficiency than lipopolysaccharide, both vesicular proteins and lipopolysaccharide are crucial in MOMVs-mediated protection.ConclusionsThe multi-serogroup nanovesicles produced by APEC strains will open up a new way for the development of next generation vaccines with low toxicity and broad protection in the treatment and control of APEC infection.

Project description:Avian pathogenic Escherichia coli (APEC) is a serious systemic infectious disease in poultry infections, causing severe economic losses to the poultry industry. Previous studies have shown that secretion of virulence proteins was required for the pathogenicity of APEC through the secretion system. Outer membrane vesicles (OMVs) are a generalized secretion system of Gram-negative bacteria that play a key role in the long-distance delivery of virulence factors, but whether they are associated with the pathogenic mechanism of APEC has not been determined. In this study, OMVs were purified and characterized from AE17 (O2 serotype) by ultracentrifugation and density gradient centrifugation and their protein cargo was identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, 89Zr was labeled after chelating AE17 OMVs by DFO and positron emission tomography PET imaging was used to track 89Zr-DFO-OMVs in chickens and to pathologically analyze the distribution sites. This study showed that AE17 OMVs were membrane vesicles ranging in size from 20 to 200 nm and proteomic analysis revealed the presence of virulence proteins, including adhesion proteins OmpA, OmpC, OmpF, OmpX, FimH, FimC and FigE, and serum resistance proteins OmpT and MliC and immune response regulator proteins (FliC). In addition, in vivo PET imaging to track the biodistribution of AE17 OMVs showed that AE17 OMVs were taken up by the lung region and the gastrointestinal and renal regions but were not detected in other areas. Pathological analysis of the tissue sites where AE17 OMVs were ingested showed inflammatory responses and damage. These findings suggested that AE17 OMVs not only contained a group of virulence proteins associated with AE17 infection but can also deliver these virulence proteins over long distances and caused tissue inflammatory damage. Our study revealed a previously unidentified causative microbial signal in the pathogenesis of APEC that could aid in the development of vaccines and antibiotics effective against APEC.

Dataset Information

Comparative study of pathogenic and non-pathogenic Escherichia coli outer membrane vesicles and prediction of host-interactions with TLR signaling pathways.

Objective

Results

Publications

Comparative study of pathogenic and non-pathogenic Escherichia coli outer membrane vesicles and prediction of host-interactions with TLR signaling pathways.

Similar Datasets

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