ArticleGastroenterology2012
Vacuolating cytotoxin and variants in Atg16L1 that disrupt autophagy promote Helicobacter pylori infection in humans.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 1 of them a synthesis that pooled it.
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Who cites it
127 citing papers in PubMed, 1 synthesis or guideline pooled it, 243 citations in OpenAlex.
- Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025Pooled it
- Internalization ofAnnals of medicine · 2026Review
- Autophagy: Mechanisms and therapeutic perspectives in intestinal metaplasia (Review).Molecular medicine reports · 2026Review
- Avian pathogenic Escherichia coli virulence protein Hcp2a induces incomplete autophagy in chicken HD11 cells.Poultry science · 2026Article
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- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- rIL-22 Alleviates Severe Acute Pancreatitis and Secondary Multiple Organ Injury Induced by Caerulein in Mice.Inflammation · 2026Article
- Pathogenicity and virulence ofVirulence · 2025Review
- Review
- Inflammasomes and autophagy in cancer: unlocking targeted therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Deciphering the dual role of autophagy in gastric cancer and gastroesophageal junction cancer: from tumor suppression to cancer progression.Discover oncology · 2025Review
- Prevalence of H. Pylori in inflammatory bowel disease patients and its association with severity.BMC gastroenterology · 2025Article
- Vacuolating Cytotoxin A (VacA) and Extracellular Vesicles inIranian journal of pathology · 2025Review
- Autophagy and its role in gastrointestinal diseases.World journal of gastroenterology · 2024Article
- A Narrative Review: Immunometabolic Interactions of Host-Gut Microbiota and Botanical Active Ingredients in Gastrointestinal Cancers.International journal of molecular sciences · 2024Review
- An antibiotic-free platform for eliminating persistentActa pharmaceutica Sinica. B · 2024Article
- Exploring the Link betweenAntibiotics (Basel, Switzerland) · 2024Review
- Review
- Regulation of regulatory T cells and tumor-associated macrophages in gastric cancer tumor microenvironment.Cancer medicine · 2024Review
- Programmed cell death inFrontiers in cellular and infection microbiology · 2024Review
67 more citing papers are in PubMed but not listed here.
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23 authors at 9 institutions in 5 countries.
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Abstract
BACKGROUND &
aimsThe Helicobacter pylori toxin vacuolating cytotoxin (VacA) promotes gastric colonization, and its presence (VacA(+)) is associated with more-severe disease. The exact mechanisms by which VacA contributes to infection are unclear. We previously found that limited exposure to VacA induces autophagy of gastric cells, which eliminates the toxin; we investigated whether autophagy serves as a defense mechanism against H pylori infection.
methodsWe investigated the effect of VacA on autophagy in human gastric epithelial cells and primary gastric cells from mice. Expression of p62, a marker of autophagy, was also assessed in gastric tissues from patients infected with toxigenic (VacA(+)) or nontoxigenic strains. We analyzed the effect of VacA on autophagy in peripheral blood monocytes obtained from subjects with different genotypes of ATG16L1, which regulates autophagy. We performed genotyping for ATG16L1 in 2 cohorts of infected and uninfected subjects.
resultsProlonged exposure of human gastric epithelial cells and mouse gastric cells to VacA disrupted induction of autophagy in response to the toxin, because the cells lacked cathepsin D in autophagosomes. Loss of autophagy resulted in the accumulation of p62 and reactive oxygen species. Gastric biopsy samples from patients infected with VacA(+), but not nontoxigenic strains of H pylori, had increased levels of p62. Peripheral blood monocytes isolated from individuals with polymorphisms in ATG16L1 that increase susceptibility to Crohn's disease had reduced induction of autophagy in response to VacA(+) compared to cells from individuals that did not have these polymorphisms. The presence of the ATG16L1 Crohn's disease risk variant increased susceptibility to H pylori infection in 2 separate cohorts.
conclusionsAutophagy protects against infection with H pylori; the toxin VacA disrupts autophagy to promote infection, which could contribute to inflammation and eventual carcinogenesis.
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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.