Cag pathogenicity island-specific responses of gastric epithelial cells to
            <i>Helicobacter pylori</i>
            infection

Guillemin, Karen; Salama, Nina R.; Tompkins, Lucy S.; Falkow, Stanley

doi:10.1073/pnas.182558799

Cited by 204 publications

(170 citation statements)

References 44 publications

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“…The pathogenicity island (cag PAI) of H. pylori encodes components of a type IV secretion system that can deliver (inject) bacterial products into epithelial cells, including products linked to greater host pathology (29,45). It is remarkable that Hp1 can elicit formation of a robust immune response in our gnotobiotic mouse model given that its cag PAI has only retained ORFs 1-8 (e.g., it lacks cagA and cagE).…”

Section: Discussionmentioning

confidence: 99%

“…Our data set contained several genes involved in cholesterol biosynthesis (farnesyl diphosphate synthetase, ϩ2.9; mevalonate decarboxylase, ϩ3) that were also identified in a recent DNA microarray analysis of the responses of a cultured gastric adenocarcinoma-derived epithelial cell line (AGS) to H. pylori (29). In addition, we identified two other transcripts encoding proteins involved in modulating cholesterol efflux in macrophages that were increased in the lymphoid aggregate [ATP binding cassette (ABC) subfamily A1 (ABCA1), ϩ2.7; ABCG1, ϩ4.2].…”

Section: Molecular Characterization Of the Host Response At The Fs͞z mentioning

confidence: 99%

“…In addition, we identified two other transcripts encoding proteins involved in modulating cholesterol efflux in macrophages that were increased in the lymphoid aggregate [ATP binding cassette (ABC) subfamily A1 (ABCA1), ϩ2.7; ABCG1, ϩ4.2]. Modulating cholesterol synthesis and fluxes could play an important role in host defense by altering membrane fluidity, forming lipid rafts for signaling, increasing the levels of endotoxin neutralizing lipoprotein, and recruiting macrophages (29,30). n-LCM was used to procure cells from equivalent-sized neighboring patches of FS͞Z mucosa, one with a lymphoid aggregate, the other with a diffuse pattern of mild gastritis, from five 14-week-old ex-GF normal mice.…”

Section: Molecular Characterization Of the Host Response At The Fs͞z mentioning

confidence: 99%

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The impact of parietal cells onHelicobacter pyloritropism and host pathology: An analysis using gnotobiotic normal and transgenic mice

Syder

Guruge

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Helicobacter pylori infection of the human stomach is common and typically benign, although a subset of hosts develops severe pathology. Infection occurs in an organ with distinct microenvironments characterized by pronounced differences in the composition of acid-producing parietal cells. In this study, we examine determinants of bacterial tropism to various gastric niches by using germ-free normal and transgenic mice with an engineered parietal cell ablation. Mice were colonized for 8 weeks with a clinical isolate (Hp1) that expresses adhesins recognized by epithelial NeuAc␣2,3Gal␤1,4 glycan receptors. In normal mice, Hp1 has tropism for a parietal cell-deficient niche where sialylated glycans are expressed by a narrow band of pit cells positioned at the boundary between the squamous epithelium (forestomach) and the proximal glandular epithelium. Lymphoid aggregates that develop in this niche, but not elsewhere in the stomach, were analyzed by GeneChip and quantitative RT-PCR studies of laser capture microdissected mucosa and yielded a series of biomarkers indicative of immune cell activation and maturation. Genetic ablation of parietal cells produced a new source of NeuAc␣2,3Gal␤1,4 glycans in amplified gastric epithelial lineage progenitors, with accompanying expansion of Hp1 within the glandular epithelium. Lymphoid aggregates that develop in this formerly acid-protected epithelium have molecular features similar to those observed at the forestomach͞glandular junction. These findings demonstrate the important roles played by parietal cells and glycan receptors in determining the positioning of H. pylori within the gastric ecosystem, and emphasize the need to consider the evolution of pathology within a given host in a niche-specific context. gastric acid ͉ adhesin receptors ͉ immune response ͉ germ-free animals A t least half of all humans harbor Helicobacter pylori in their stomachs. This microaerophilic bacterium is usually acquired in childhood and remains in the stomach of its host for decades (1). In most cases, the host-microbial relationship is benign, marked only by mild mucosal inflammation. However, in a subset of individuals, this relationship evolves to produce gastric or duodenal ulcers, adenocarcinoma, or mucosal lymphoma (2).Lee and coworkers (3) have emphasized that severe pathology more often develops in regions of the gastric epithelium where there is a marked transition in the census of acid-producing parietal cells. They and others proposed that local environmental pH gradients at these transitions provide the organism with an opportunity to sample and occupy niches where growth conditions are optimal (3, 4). Once the organism becomes entrenched, pH and other niche-associated factors (e.g., redox state, nutrient availability) then presumably shape the nature of the host-microbial interaction (5).These speculations emphasize the importance of viewing the nature of the host-microbial cross-talk, the genetic microevolution of this bacterium (6, 7), and the structure of the pathogenic cascad...

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Section: Discussionmentioning

confidence: 99%

Section: Molecular Characterization Of the Host Response At The Fs͞z mentioning

confidence: 99%

Section: Molecular Characterization Of the Host Response At The Fs͞z mentioning

confidence: 99%

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The impact of parietal cells onHelicobacter pyloritropism and host pathology: An analysis using gnotobiotic normal and transgenic mice

Syder

Guruge

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Gene Ontology categories for kinases and transcription factors were among the most rapidly degraded mRNAs in both humans and yeast, and transcripts encoding ribosomal and core metabolic proteins were extremely stable in both organisms. Searching the human database with the yeast rpb1 profiles yielded experiments that may correspond to transcriptional blockade: profiles of host responses to diverse pathogenic infections [28][29][30][31] and profiles from whole blood, which is dominated by mRNAs from erythrocytes, which lack nuclei and therefore do not carry out transcription 32 .…”

Section: Biological Processesmentioning

confidence: 99%

Comparing genomic expression patterns across species identifies shared transcriptional profile in aging

et al. 2004

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We developed a method for systematically comparing gene expression patterns across organisms using genome-wide comparative analysis of DNA microarray experiments. We identified analogous gene expression programs comprising shared patterns of regulation across orthologous genes. Biological features of these patterns could be identified as highly conserved subpatterns that correspond to Gene Ontology categories. Here, we demonstrate these methods by analyzing a specific biological process, aging, and show that similar analysis can be applied to a range of biological processes. We found that two highly diverged animals, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, implement a shared adult-onset expression program of genes involved in mitochondrial metabolism, DNA repair, catabolism, peptidolysis and cellular transport. Most of these changes were implemented early in adulthood. Using this approach to search databases of gene expression data, we found conserved transcriptional signatures in larval development, embryogenesis, gametogenesis and mRNA degradation.Gene expression profiling measures the expression levels of thousands of genes at once 1,2 . Most expression profiling studies have focused on the specific genes that respond to specific conditions, but another important direction in functional genomics is to derive insight from global patterns of gene expression. Genome-scale expression patterns have been used as physiological 'fingerprints' for classifying tumors 3,4 and assigning uncharacterized mutations and drugs to known pathways 5 . Because they use information from many genes at once, patterns have great discriminating power, even when the transcriptional effects on individual genes are small 5,6 .The patterns of changes in gene expression observed in microarray experiments can be extensive and complex. To try to analyze these patterns, we exploited the principle that important biological processes are often conserved between organisms. We present an approach to comparative functional genomics based on shared patterns of regulation across orthologous genes. We also present a method for identifying conserved biological components of those patterns that correspond to Gene Ontology categories. These methods can be used to search databases of microarray experiments to discover connections among biological processes in different organisms. RESULTS Comparing genomic expression patterns across speciesWe used phylogenetic analysis to systematically identify orthologous groups of genes for all pairwise comparisons between C. elegans, D. melanogaster, Saccharomyces cerevisiae and Homo sapiens (Supplementary Tables 1-5 online). For C. elegans and D. melanogaster, we identified 3,851 most-conserved orthologous gene pairs (Fig. 1a).We used DNA microarrays in each organism to compare gene expression under different conditions (Fig. 1b). We then used gene phylogenetic relationships to match systematically the measurements of differential expression between orthologous genes from the tw...

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“…In this way, CagA protein can get inside the host cells and stimulate cell signalling through interaction with several host proteins. This interaction leads to increased cytokine and regulatory molecule production (Guillemin et al 2002) and could be related to initiation of tumour transformation (Segal 1997;Tummala et al 2004;Hatakeyama 2006). VacA is another important H. pylori virulence factor.…”

Section: H Pylori Virulence Factorsmentioning

confidence: 99%

Helicobacter pylori – Not Only a Gastric Pathogene?

Lukeš¹,

Astl²,

Pavlík³

et al. 2011

Peptic Ulcer Disease

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Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection

Cited by 204 publications

References 44 publications

The impact of parietal cells onHelicobacter pyloritropism and host pathology: An analysis using gnotobiotic normal and transgenic mice

The impact of parietal cells onHelicobacter pyloritropism and host pathology: An analysis using gnotobiotic normal and transgenic mice

Comparing genomic expression patterns across species identifies shared transcriptional profile in aging

Helicobacter pylori – Not Only a Gastric Pathogene?

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