Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA244596 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Helicobacter pylori conquered the world by colonizing the human stomach. There are two major groups of strains, one with and one without a cag pathogenicity island (cagPAI), which result in different clinical outcomes with increased severity in cagPAI+ H. pylori infections such as higher inflammation and higher rates of gastric carcinogenesis. Since the gastro-intestinal tract is bombarded with nonspecific ligands that would induce innate signaling, tissue-resident immune cells are believed to lack toll-like receptor (TLR) signaling (anergy).To illuminate how anergic innate immune cells respond to H. pylori, we first investigated the transcriptome of H. pylori infected wild type and MyD88/Trif -/- macrophages, which lack TLR signaling. We observed that the majority of regulated genes in wt macrophages were dependent on TLR signaling. In addition, we found that some of the upregulated genes changed their kinetic behavior depending on TLR signaling. Only anergic macrophages were able to differentiate between cagPAI+ and cagPAI- H. pylori via their transcriptional kinetics of specific early response genes. These genes showed a strong bias towards adenylate-uridylate-rich elements (AREs) containing genes, including the prominent pro-inflammatory cytokines IL-1beta and TNF-alpha. Differentiation was dependent on the presence of the cag type 4 secretion system (cagT4SS), but not the CagA effector protein. Thus, we speculate that the direct recognition of the secretion system by tissue-resident macrophages enables the host to differentiate between pathogenic (cagPAI+) and commensal (cagPAI-) H. pylori variants. Microarray experiments were performed as dual-color hybridizations on Agilent mouse whole genome catalog 44K arrays. To compensate for dye-specific effects, a dye-reversal color-swap was applied. Cells were analyzed at 1h and 3h post infection
2015-09-01 | E-GEOD-56791 | biostudies-arrayexpress
Project description:Helicobacter pylori conquered the world by colonizing the human stomach. There are two major groups of strains, one with and one without a cag pathogenicity island (cagPAI), which result in different clinical outcomes with increased severity in cagPAI+ H. pylori infections such as higher inflammation and higher rates of gastric carcinogenesis. Since the gastro-intestinal tract is bombarded with nonspecific ligands that would induce innate signaling, tissue-resident immune cells are believed to lack toll-like receptor (TLR) signaling (anergy).To illuminate how anergic innate immune cells respond to H. pylori, we first investigated the transcriptome of H. pylori infected wild type and MyD88/Trif -/- macrophages, which lack TLR signaling. We observed that the majority of regulated genes in wt macrophages were dependent on TLR signaling. In addition, we found that some of the upregulated genes changed their kinetic behavior depending on TLR signaling. Only anergic macrophages were able to differentiate between cagPAI+ and cagPAI- H. pylori via their transcriptional kinetics of specific early response genes. These genes showed a strong bias towards adenylate-uridylate-rich elements (AREs) containing genes, including the prominent pro-inflammatory cytokines IL-1beta and TNF-alpha. Differentiation was dependent on the presence of the cag type 4 secretion system (cagT4SS), but not the CagA effector protein. Thus, we speculate that the direct recognition of the secretion system by tissue-resident macrophages enables the host to differentiate between pathogenic (cagPAI+) and commensal (cagPAI-) H. pylori variants.
2015-09-01 | GSE56791 | GEO
Project description:The innate immune response against Helicobacter pylori is mainly controlled by pattern recognition receptors that lead to the up-regulation of pro-inflammatory cytokines. A new player in this field is the miR-155 being regulated by TLR ligands in monocytic derived cells influencing certain intracellular pathways by down-regulating targets involved in signaling and development. By using primary bone marrow derived macrophages (BMMs) from mice deficient in the key TLR signals the regulation of miR-155 was explored. Further on the biological impact of a lack of miR-155 in BMMs was analyzed by micro-array studies and apoptosis assays. We observed that miR-155 is up-regulated in response to H. pylori via TLR2 and TLR4 in a NF-M-NM-:B dependent manner, but also identified a TLR2/TLR4 independent mechanism that was strongly connected to a functional TypeIV secretion system. Down-stream the high expression of miR-155 down-regulated many mRNA targets during H. pylori infection. Thereby we could validate Tspan14, Lpin1, and Pmaip1 as new targets of miR-155 and identified their binding site. These and other already published targets showed a substantial pro-apoptotic potential. We observed that H. pylori infected wild type BMMs were much more resistant to DNA damage induced apoptosis by cisplatin when compared to their respective miR-155-/- BMMs. Our data strongly suggests that there is an additional innate immune mechanism of BMMs leading to the upregulation of the anti-apoptotic miR-155 that causes resistance to DNA damage in BMMs. Microarray experiments were performed as dual-color hybridizations. To compensate for dye-specific effects, an independent dye-reversal color-swap was applied. Bone marrow derived macrophages were 'in vitro' infected with H.pylori P12 and the expression changes were measured.
2012-04-02 | E-GEOD-29388 | biostudies-arrayexpress
Project description:Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been reported to exert beneficial effects as a supplement during H. pylori eradication therapy. In the present study, we applied whole genome microarray analysis to compare the immune response induced in murine bone marrow derived macrophages (BMDM) stimulated with L. acidophilus, H. pylori, or with both bacteria in combination Microarray expression profiling was performed to analyze stimulation of bone marrow derived macrophages with Helicobacter pylori 251, Lactobacillus acidophilus NCFM or Lactobacillus acidophilus NCFM co-stimulated with Helicobacter pylori 251 were analyzed 5 hours after infection.
2013-07-02 | E-GEOD-42622 | biostudies-arrayexpress
Project description:Cag type IV secretion system (CagT4SS) mediates the translocation of a wide spectrum of substrates including oncoprotein CagA to host cells and plays an indispensable role in the pathogenesis of Helicobacter pylori. Central cylinder components, including CagM, CagX and CagY, are responsible for initiating the assembly of CagT4SS. Here, we performed differential HDX-MS analysis on CagM-CagX complex to map the interface upon binding. Our findings reveal the conformational changes of CagM and CagX during assembly.
2026-06-14 | PXD075968 | Pride
Project description:Cag type IV secretion system (CagT4SS) mediates the translocation of a wide spectrum of substrates including oncoprotein CagA to host cells and plays an indispensable role in the pathogenesis of Helicobacter pylori. Central cylinder components, including CagM, CagX and CagY, are responsible for initiating the assembly of CagT4SS. Here, we performed differential HDX-MS analysis on CagX-CagY complex to map the interface upon binding. Our findings reveal the conformational changes of CagX and CagY during assembly.
2026-06-14 | PXD075970 | Pride
Project description:The innate immune response against Helicobacter pylori is mainly controlled by pattern recognition receptors that lead to the up-regulation of pro-inflammatory cytokines. A new player in this field is the miR-155 being regulated by TLR ligands in monocytic derived cells influencing certain intracellular pathways by down-regulating targets involved in signaling and development. By using primary bone marrow derived macrophages (BMMs) from mice deficient in the key TLR signals the regulation of miR-155 was explored. Further on the biological impact of a lack of miR-155 in BMMs was analyzed by micro-array studies and apoptosis assays. We observed that miR-155 is up-regulated in response to H. pylori via TLR2 and TLR4 in a NF-κB dependent manner, but also identified a TLR2/TLR4 independent mechanism that was strongly connected to a functional TypeIV secretion system. Down-stream the high expression of miR-155 down-regulated many mRNA targets during H. pylori infection. Thereby we could validate Tspan14, Lpin1, and Pmaip1 as new targets of miR-155 and identified their binding site. These and other already published targets showed a substantial pro-apoptotic potential. We observed that H. pylori infected wild type BMMs were much more resistant to DNA damage induced apoptosis by cisplatin when compared to their respective miR-155-/- BMMs. Our data strongly suggests that there is an additional innate immune mechanism of BMMs leading to the upregulation of the anti-apoptotic miR-155 that causes resistance to DNA damage in BMMs.
2012-04-03 | GSE29388 | GEO
Project description:Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been reported to exert beneficial effects as a supplement during H. pylori eradication therapy. In the present study, we applied whole genome microarray analysis to compare the immune response induced in murine bone marrow derived macrophages (BMDM) stimulated with L. acidophilus, H. pylori, or with both bacteria in combination
2013-07-02 | GSE42622 | GEO
Project description:Based on preliminary data demonstrating that macrophages are critical regulators of Helicobacter pylori colonization and gastric pathology in mice, we sought to investigate how macrophages may serve as bacterial reservoirs of intracellular H. pylori.
2017-02-10 | GSE67270 | GEO
Project description:In this study, a whole-genome CombiMatrix Custom oligonucleotide tiling microarray with 90000 probes covering six sequenced Helicobacter pylori(H. pylori) genomes was designed and utilized for comparative genomic profiling of eight unsequenced strains isolated from patients with different gastroduodenal diseases in Heilongjiang province of China. Since significant genomic variation were found among these strains, an additional 76 H. pylori stains with different clinical outcomes isolated from various provinces of China were further tested by PCR to demonstrate this distinction. We observed several highly variable regions among strains of gastritis, gastric ulceration and gastric cancer. They are involved in genes associated with bacterial type I, type II and type III R-M system as well as in a virB gene neighboring the well studied cag pathogenic island. Previous studies have reported the diverse genetic characterization of this pathogenic island, but it is conserved in the strains tested by microarray in this study. Moreover, a number of genes involved in the type IV secretion system related to DNA horizontal transfer between H. pylori strains were identified based on the comparative analysis of the strain specific genes. These findings may provide new insights for discovering biomarkers for prediction of gastric diseases.
2013-11-10 | GSE32107 | GEO