CagA-specific gastric CD8+ tissue-resident T cells control Helicobacter pylori during the early infection phase
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA896149 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22105607_1.fastq.gz | Fastqsanger.gz | |||
| SRR22105607_2.fastq.gz | Fastqsanger.gz | |||
| SRR22105608_1.fastq.gz | Fastqsanger.gz | |||
| SRR22105608_2.fastq.gz | Fastqsanger.gz | |||
| SRR22105609_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 10 |
Similar Datasets
Project description:Infection with Helicobacter pylori strongly impacts global health by causing chronic gastritis, ulcer disease and gastric cancer. Although extensive research into the strong immune response against this persistently colonizing bacterium exists, the specific role of CD8+ T cells remains elusive. We comprehensively characterize gastric H. pylori-specific CD8+ T cell responses in mice and humans. We define CD8+ T cell populations bearing a tissue-resident memory (TRM) phenotype, which infiltrate the gastric mucosa shortly after infection and mediate pathogen control by executing antigen-specific effector properties. These induced CD8+ TRM cells show a skewed T cell receptor beta chain usage and are specific for CagA, the distinctive oncoprotein injected by H. pylori into host cells. As the infection progresses, we observe a loss of the TRM phenotype and replacement of CD8+ by CD4+ T cells, indicating a shift in the immune response during the chronic infection phase. Our results point towards a hitherto unknown role of CD8+ T cell response in this bacterial infection, which may have important clinical implications for treatment and vaccination strategies against H. pylori.
2022-12-17 | GSE216894 | GEO
Project description:The human gastric epithelium forms highly organized gland structures with different subtypes of cells. The carcinogenic bacterium Helicobacter pylori can attach to gastric cells and subsequently translocate its virulence factor CagA, but the possible host cell tropism of H. pylori is currently unknown. Here, we report that H. pylori preferentially attaches to differentiated cells in the pit region of gastric units. Single-cell RNA-seq shows that organoid-derived monolayers recapitulate the pit region, while organoids capture the gland region of the gastric units. Using these models, we show that H. pylori preferentially attaches to highly differentiated pit cells, marked by high levels of GKN1, GKN2 and PSCA. Directed differentiation of host cells enable enrichment of the target cell population and confirm H. pylori preferential attachment and CagA translocation into these cells. Attachment is independent of MUC5AC or PSCA expression, and instead relies on bacterial TlpB-dependent chemotaxis towards host cell-released urea, which scales with host cell size.
2022-08-20 | GSE167561 | GEO
Project description:Helicobacter pylori(H. pylori), a gastrointestinal pathogen, is known to increase the risk of gastric cancer by activating chronic pro-inflammatory signaling pathways in epithelial cells. Cytotoxin-related protein A (CagA) is known to play an important role in gastric cancer development. CagA has been reported to induce tumors by inducing overexpression of YAP/TAZ, a component of Hippo signaling, and dysregulation of the pathway, thereby promoting cell proliferation and resistance to apoptosis. However, the role of H.pylori-mediated YAP/TAZ has not yet been fully investigated. Our study aimed to investigate the role of YAP/TAZ in H.pylori-mediated Hippo pathway dysregulation in gastric carcinogenesis using H.pylori-infected gastric cancer cell lines, knockout mice, and patient-derived organoids. CagA-mediated YAP overexpression in gastric epithelial cells induced intestinal epithelial metaplasia and induced intracellular rearrangement of the binding protein ZO1, thereby conferring cell motility.
2024-10-28 | GSE275727 | GEO
Project description:H. pylori infection of human gastric epithelial cells (GEC) represses H,K-ATPase alpha subunit (HK-alpha) gene transcription through NF-Kappa B p50 homodimer binding to HK-alpha promoter. The bacterial cagA and slt gene products have been implicated in HK-alpha repression, which facilitates gastric H. pylori colonization and may underlie transient clinical hypochlorhydria. We hypothesized that H. pylori also regulates H,K-ATPase expression post-transcriptionally by micro-RNA interaction with HK-alpha mRNA. Our microarray experiment examined the effect of infection by wildtype H. pylori infection or a delta-cagA H. pylori mutant on miRNA expression of human gastric cells (AGS). Our results indicate that H. pylori infection up-regulates GEC miRNAs that target the HK-alpha 3' UTR and block translation, and that CagA activity is implicated in the miRNA up-regulation.
2016-01-18 | GSE51306 | GEO
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
Project description:H. pylori infection of human gastric epithelial cells (GEC) represses H,K-ATPase alpha subunit (HK-alpha) gene transcription through NF-Kappa B p50 homodimer binding to HK-alpha promoter. The bacterial cagA and slt gene products have been implicated in HK-alpha repression, which facilitates gastric H. pylori colonization and may underlie transient clinical hypochlorhydria. We hypothesized that H. pylori also regulates H,K-ATPase expression post-transcriptionally by micro-RNA interaction with HK-alpha mRNA. Our microarray experiment examined the effect of infection by wildtype H. pylori infection or a delta-cagA H. pylori mutant on miRNA expression of human gastric cells (AGS). Our results indicate that H. pylori infection up-regulates GEC miRNAs that target the HK-alpha 3' UTR and block translation, and that CagA activity is implicated in the miRNA up-regulation. Three types of samples were generated for microarray analysis: 1) AGS cells infected with wildtype H. pylori; 2) AGS cells infected with cagA-deficient H. pylori; 3) a mock-infected sample, prepared as a control by combining total RNA from uninfected AGS cells with total RNA from wildtype H. pylori, with relative eukaryotic and prokaryotic RNA amounts matching those observed in infected samples, based on proportional ribosomal peak heights quantified by Bioanalyzer. Three experimental replicates were generated for each type of treatment.
2016-01-18 | E-GEOD-51306 | biostudies-arrayexpress
Project description:Helicobacter pylori (H. pylori) infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology is unknown. Here we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a-/-, Angptl4-/-, Il17a-/-Angptl4-/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation through binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.
2024-05-15 | GSE266891 | GEO
Project description:Helicobacter pylori are gram-negative bacteria that colonize the human stomach and are the major etiological factor in gastric carcinoma development. The aim of this work was to evaluate changes in gene expression in gastric cells induced by H. pylori.
2016-03-01 | GSE70394 | GEO
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.
2010-11-13 | GSE21833 | GEO
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