Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Interfering with interferons: cholesterol modification by Helicobacter pylori prevents IFN receptor assembly

ABSTRACT: Interferons (IFNs) are thought to primarily protect against intracellular pathogens. Here we show that Helicobacter pylori, a chronic colonizer of gastric mucosal surfaces, effectively blocks both type I and type II IFN signalling via cholesterol-α-glucosyltransferase (CaGT). Thus, CaGT, causing depletion of cholesterol from host cells, prevents infected epithelial cells from executing crucial effector functions, including the production of human b-defensin 3 (hBD3). Cholesterol depletion by CaGT prevents the assembly of interferon receptors resulting in a failure of JAK/STAT1 activation and subsequent expression of downstream transcriptional regulators (IRF-1 and 7), T-cell chemo-attractants (CXCL9 and 10) and antimicrobial peptides. Moreover, infection of human primary gastric epithelial cells by H. pylori also prevents residual type I IFN autocrine signalling and thereby further dampens the response to type II IFNs. Our results uncover a cooperative role for type I and type II IFNs in the defense against extracellular bacteria and explain the mechanism by which cholesterol modification by H. pylori usurps epithelial cell effector function, normally triggered by T-cell-derived inflammatory signals. Accordingly, CaGT acts as a central pathogenesis determinant and immune modulator of H. pylori contributing to this pathogen's exceptional ability of life-long persistence.

ORGANISM(S): Homo sapiens

PROVIDER: GSE76589 | GEO | 2018/03/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Sugar turns benefit of cholesterol into immune evasion in Helicobacter pylori infected C57BL/6 mice

Project description:Following the initial demonstration of Helicobacter pyloriâ??s pathogenic potential, evidence has been accumulated that H. pylori is the leading cause of gastric ulcers, carcinoma and lymphoma3. Cholesterol is a physiological constituent of membranes critical for their biophysical properties, but is stigmatised as mediating detrimental effects in obesity and cardiovascular disease. Since H. pylori is auxotrophic for cholesterol, we explored the assimilation of cholesterol by H. pylori upon infection. Here we show that H. pylori follows a cholesterol gradient and extracts the lipid from plasma membranes of epithelial cells for subsequent glycosylation. Cholesterol promotes phagocytosis of H. pylori by antigen-presenting cells such as macrophages and dendritic cells and enhances antigen-specific T cell responses. Consistently, cholesterol-rich diet during bacterial challenge leads to a reduction of the H. pylori burden in the stomach. Intrinsic a-glycosylation of cholesterol abrogates phagocytosis of H. pylori and subsequent T cell activation. Hence, we propose a novel mechanism regulating host-pathogen interaction which describes glycosylation of a lipid tipping the scales towards immune evasion or response. color-swap dye-reversal hybridizations

2010-06-30 | E-GEOD-3878 | biostudies-arrayexpress

Sugar turns benefit of cholesterol into immune evasion in Helicobacter pylori infected C57BL/6 mice

Project description:Following the initial demonstration of Helicobacter pylori’s pathogenic potential, evidence has been accumulated that H. pylori is the leading cause of gastric ulcers, carcinoma and lymphoma3. Cholesterol is a physiological constituent of membranes critical for their biophysical properties, but is stigmatised as mediating detrimental effects in obesity and cardiovascular disease. Since H. pylori is auxotrophic for cholesterol, we explored the assimilation of cholesterol by H. pylori upon infection. Here we show that H. pylori follows a cholesterol gradient and extracts the lipid from plasma membranes of epithelial cells for subsequent glycosylation. Cholesterol promotes phagocytosis of H. pylori by antigen-presenting cells such as macrophages and dendritic cells and enhances antigen-specific T cell responses. Consistently, cholesterol-rich diet during bacterial challenge leads to a reduction of the H. pylori burden in the stomach. Intrinsic a-glycosylation of cholesterol abrogates phagocytosis of H. pylori and subsequent T cell activation. Hence, we propose a novel mechanism regulating host-pathogen interaction which describes glycosylation of a lipid tipping the scales towards immune evasion or response. Keywords: disease state analysis

2005-12-22 | GSE3878 | GEO

Expression data from AGS cells with Helicobacter pylori infection

Project description:Helicobacter pylori (H. pylori) is a human pathogen that infects almost half of the world’s population. Infection with H. pylori is frequently associated with chronic gastritis and can even lead to gastric and duodenal ulcers and gastric cancer. Although the persistent colonization of H. pylori and the development of H. pylori-associated gastritis remain poorly understood, it is believed that, in gastric mucosa, the modulated gastric epithelial cells (GECs) by H. pylori are key contributors. We used microarrays to detail the global programme of gene expression in Helicobacter pylori infected-gastric epithelial cell line AGS cells and identified up-regulated genes induced by Helicobacter pylori infection.

2024-04-18 | GSE264263 | GEO

Ornithine Decarboxylase in Gastric Epithelial Cells Promotes the Immunopathogenesis of Helicobacter pylori Infection

Project description:Colonization by H. pylori is associated with a wide range of gastric diseases, ranging from superficial gastritis to more severe pathologies, including intestinal metaplasia and adenocarcinoma. The interplay of the host response and the pathogen affect the outcome of disease. One major component of the mucosal response to H. pylori is the activation of a strong, but inefficient immune response that fails to control the infection and frequently causes tissue damage. We have shown that polyamines can regulate H. pylori-induced inflammation. Chemical inhibition of ornithine decarboxylase (ODC), which generates putrescine from L-ornithine, reduces gastritis in mice and adenocarcinoma incidence in gerbils infected with H. pylori. However, we have also demonstrated that Odc deletion in myeloid cells enhances M1 macrophage activation and gastritis. Here we used a genetic approach to assess the specific role of gastric epithelial ODC during H. pylori infection. Deletion of Odc in gastric epithelial cells reduces gastritis, attenuates epithelial proliferaton, alters the metabolome, and dowregulates the expression of immune mediators induced by H. pylori. Inhibition of ODC activity in gastric epithelial cells reduces H. pylori-induced NF-B activation and CXCL8 mRNA expression. Chronic inflammation is a major risk factor for the progression to more severe pathologies associated with H. pylori infection and we now show that epithelial ODC plays an important role in mediating this inflammatory response.

2022-06-15 | MTBLS3235 | MetaboLights

Expression data from Helicobacter pylori-infected mouse gastric epithelial progenitor and non-progenitor cells.

Project description:Helicobacter pylori clinical isolates can establish themselves in gastric epithelial stem cells and this interaction may have implications for gastric tumorigenesis. Mouse gastric epithelial progenitor cells (mGEPs) and non-progenitor gastric epithelial cells (npGECs) were infected for 24hrs with Helicobacter pylori clinical isolates Kx1 and Kx2. Kx1 was isolated from a patient with chronic atrophic gastritis (ChAG) and Kx2 from the same patient 4 years later, when he progressed to gastric adenocarcinoma. Keywords: RNA Expression Array

2008-02-22 | GSE10262 | GEO

Gene expression changes in gastric epithelial cells induced by Helicobacter pylori infection

Project description:This group is focusing on the molecular mechanisms of the biosynthesis of glycoconjugates and carbohydrate ligands important in the process of gastric carcinogenesis and on gastric carcinoma progression and metastasis. The adhesion of H. pylori to epithelial cells induces a variety of modifications, including changes in cell morphology,cytokine production and release, alterations in glycosylation and in the biosynthesis of mucins. This study aims to identify the gene expression changes in the gastric epithelial cells (AGS) induced by Helicobacter pylori infection. This experiment was performed as previously described in the literature by submitting a gastric cell line to co-culture with reference strains of H. pylori. The following RNA samples (in triplicate) were analyzed by hybridization to the GLYCOv2 array: 1)Gastric cell line co-culture with H. pylori strain A(High Patogenicity) 2)Gastric cell line co-culture with H. pylori strain B(Low Patogenicity) 3)Gastric cell line without H. pylori co-culture (control)

2011-02-17 | E-GEOD-27347 | biostudies-arrayexpress

Helicobacter pylori colonization ameliorates glucose homeostasis in mice

Project description:Background: Helicobacter pylori has been shown to alter the secretion of gastric hormones that modulate body fat deposition. Since cag-positive H. pylori strains interact intimately with the host gastric epithelial cells and trigger higher inflammation than cag-negative strains, we hypothesized that gastric colonization with H. pylori strains without functional cagA ameliorates obesity and its complications by modulating gastric gene expression and inflammation. Methodology/Principal Findings: To test this hypothesis we examined the effects of gastric colonization on metabolic and inflammatory markers in mice infected with two isogenic strains of H. pylori: 26695 strain 98-325 (cagA+ wild-type) and its cag pathogenicity island (cagPAI) mutant strain 99-305, a knockout made by inserting a chloramphenicol resistance cassette. Only the cagPAI mutant decreased fasting blood glucose levels, improved glucose tolerance and suppressed weight gain in db/db mice and mice with diet-induced obesity. These effects were associated with increased gastric leptin levels, suppressed infiltration of macrophages, enhanced influx of regulatory T cells (Treg) in adipose tissue and suppressed gastric inflammation. Gene set enrichment analyses of gastric mucosal samples identified six differentially modulated pathways, including the Hedgehog signaling pathway that is associated with control of cellular proliferation and gastric carcinogenesis as well as the insulin signaling pathway. Conclusions/Significance: Gastric colonization with cagPAI-negative strains of H. pylori ameliorate obesity and inflammation by modulating gastric gene expression, suggesting that cag-negative H. pylori strains might be beneficial in ameliorating obesity and its co-morbidities. Gastric mucosa from three groups of mice: uninfected, infected with H. pylori 26695 strain 98-325 (cagA+ wild-type) or infected with H. pylori mutant strain 99-305 (lacking cag pathogenicity island; cagA-)

2010-11-13 | E-GEOD-21833 | biostudies-arrayexpress

Response of gastric epithelial progenitors to H. pylori isolates from Swedish patients with chronic atrophic gastritis

Project description:This SuperSeries is composed of the following subset Series: GSE16390: Response of gastric epithelial progenitors to H. pylori isolates from Swedish patients with chronic atrophic gastritis 1 GSE16439: Response of gastric epithelial progenitors to H. pylori isolates from Swedish patients with chronic atrophic gastritis 2 Refer to individual Series

2009-10-26 | E-GEOD-16440 | biostudies-arrayexpress

Membrane substrates of HtrA from Helicobacter pylori

Project description:High temperature requirement A (HtrA) is a serine protease secreted by the group-I carcinogen Helicobacter pylori (H. pylori). The human cell adhesion protein and tumor suppressor E-cadherin (hCdh1) expressed on the surface of gastric epithelial cells was identified as the first HtrA substrate. HtrA-mediated hCdh1 cleavage and subsequent disruption of intercellular adhesion are considered as important steps in H. pylori pathogenesis. In this study, we performed a proteomic profiling of H. pylori HtrA (HpHtrA) to decipher the complex mechanism how H. pylori can interfere with epithelial barrier integrity.

2022-02-17 | PXD025360 | Pride

microRNA expressions in gastric cancer

Project description:The study was undertaken to identify microRNAs differently expressed by intestinal type of gastric cancer using miRNA microarray. The miRNA expression in the intestinal type of gastric cancer depending on H. pylori infection suggest that different gastric cancer pathogenesis could be exist between H. pylori-positive and -negative gastric cancer.

2014-01-25 | GSE54397 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data