ArticleProceedings of the National Academy of Sciences of the United States of America2013
Helicobacter pylori γ-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
120 citing papers in PubMed, 2 syntheses or guidelines pooled it, 225 citations in OpenAlex.
- Association Between Helicobacter pylori Exposure and Decreased Odds of Eosinophilic Esophagitis-A Systematic Review and Meta-analysis.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2019Pooled it
- Systematic review with meta-analysis: association between Helicobacter pylori CagA seropositivity and odds of inflammatory bowel disease.Alimentary pharmacology & therapeutics · 2019Pooled it
- HistologicalDEN open · 2027Article
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- Transplacental Antimicrobial Antibodies and Childhood Asthma: Maternal Nativity as an Upstream Factor.Allergy · 2026Article
- Mucosal vaccination with enzymatically activeFrontiers in microbiology · 2026Article
- Pathogenicity and virulence ofVirulence · 2025Review
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- Effect ofImmunotherapy · 2025Review
- Advances in Helicobacter pylori lipopolysaccharide structure and function.FEMS microbiology reviews · 2025Review
- Regulatory T cells and their role in allergic disease.Allergy · 2025Review
- Developing a potent vaccine againstExpert reviews in molecular medicine · 2024Review
- Novel multiphoton intravital imaging enables real-time study of Helicobacter pylori interaction with neutrophils and macrophages in the mouse stomach.PLoS pathogens · 2024Article
- Article
- Glutathione‑degrading enzymes in the complex landscape of tumors (Review).International journal of oncology · 2024Review
- Critical role of the gut microbiota in immune responses and cancer immunotherapy.Journal of hematology & oncology · 2024Review
- Structural Analysis of Membrane-associated Forms of Helicobacter pylori VacA Toxin.Journal of molecular biology · 2024Article
- Update on the association between Helicobacter pylori infection and asthma in terms of microbiota and immunity.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2024Review
- Microbes little helpers and suppliers for therapeutic asthma approaches.Respiratory research · 2024Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Infection with the gastric bacterial pathogen Helicobacter pylori is typically contracted in early childhood and often persists for decades. The immunomodulatory properties of H. pylori that allow it to colonize humans persistently are believed to also account for H. pylori's protective effects against allergic and chronic inflammatory diseases. H. pylori infection efficiently reprograms dendritic cells (DCs) toward a tolerogenic phenotype and induces regulatory T cells (Tregs) with highly suppressive activity in models of allergen-induced asthma. We show here that two H. pylori virulence determinants, the γ-glutamyl transpeptidase GGT and the vacuolating cytotoxin VacA, contribute critically and nonredundantly to H. pylori's tolerizing effects on murine DCs in vitro and in vivo. The tolerance-promoting effects of both factors are independent of their described suppressive activity on T cells. Isogenic H. pylori mutants lacking either GGT or VacA are incapable of preventing LPS-induced DC maturation and fail to drive DC tolerization as assessed by induction of Treg properties in cocultured naive T cells. The Δggt and ΔvacA mutants colonize mice at significantly reduced levels, induce stronger T-helper 1 (Th1) and T-helper 17 (Th17) responses, and/or trigger more severe gastric pathology. Both factors promote the efficient induction of Tregs in vivo, and VacA is required to prevent allergen-induced asthma. The defects of the Δggt mutant in vitro and in vivo are phenocopied by pharmacological inhibition of the transpeptidase activity of GGT in all readouts. In conclusion, our results reveal the molecular players and mechanistic basis for H. pylori-induced immunomodulation, promoting persistent infection and conferring protection against allergic asthma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.