ArticleGastroenterology2013
Dual oxidases control release of hydrogen peroxide by the gastric epithelium to prevent Helicobacter felis infection and inflammation in mice.
Article in Gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.Communications biology · 2021Pooled it
- Implications of bacterial exposure to reactive oxygen and chlorine species.Infection and immunity · 2026Review
- TheJournal of bacteriology · 2026Article
- Hydrogen Peroxide: A Ubiquitous Component of Beverages and Food.International journal of molecular sciences · 2025Review
- Accessible homeostatic gastric organoids reveal secondary cell type-specific host-pathogen interactions in Helicobacter pylori infections.Nature communications · 2025Article
- Single-cell profiling reveals a reduced epithelial defense system, decreased immune responses and the immune regulatory roles of different fibroblast subpopulations in chronic atrophic gastritis.Journal of translational medicine · 2025Article
- Epithelial Dual Oxidase 2 Shapes the Mucosal Microbiome and Contributes to Inflammatory Susceptibility.Antioxidants (Basel, Switzerland) · 2023Article
- Gastrointestinal redox homeostasis in ageing.Biogerontology · 2023Review
- Gut microbes involvement in gastrointestinal cancers through redox regulation.Gut pathogens · 2023Review
- Isotope tracing reveals bacterial catabolism of host-derived glutathione during Helicobacter pylori infection.PLoS pathogens · 2023Article
- Structure, regulation, and physiological functions of NADPH oxidase 5 (NOX5).Journal of physiology and biochemistry · 2023Review
- Signaling pathways of oxidative stress response: the potential therapeutic targets in gastric cancer.Frontiers in immunology · 2023Review
- High-throughput screening of caterpillars as a platform to study host-microbe interactions and enteric immunity.Nature communications · 2022Article
- Article
- IFN-induced cell-autonomous immune mechanisms in the control of intracellular protozoa.Parasitology research · 2022Review
- Efficacy and Safety of Zuojin Pill for the Treatment of Chronic Nonatrophic Gastritis: A Randomized Active-Controlled Clinical Trial.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- DUOX2 variants associate with preclinical disturbances in microbiota-immune homeostasis and increased inflammatory bowel disease risk.The Journal of clinical investigation · 2021Article
- Decoding the matrix: multiomics reveals host-microbe biomarker for inflammatory bowel disease.The Journal of clinical investigation · 2021Article
- Intestinal IL-17R Signaling Controls Secretory IgA and Oxidase Balance inJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Epithelial TLR4 Signaling Activates DUOX2 to Induce Microbiota-Driven Tumorigenesis.Gastroenterology · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsDual oxidases (DUOX) are conserved reduced nicotinamide adenine dinucleotide phosphate oxidases that produce H2O2 at the epithelial cell surface. The DUOX enzyme comprises the DUOX and DUOX maturation factor (DUOXA) subunits. Mammalian genomes encode 2 DUOX isoenzymes (DUOX1/DUOXA1 and DUOX2/DUOXA2). Expression of these genes is up-regulated during bacterial infections and chronic inflammatory diseases of the luminal gastrointestinal tract. The roles of DUOX in cellular interactions with microbes have not been determined in higher vertebrates.
methodsMice with disruptions of Duoxa1 and Duoxa2 genes (Duoxa(-/-) mice) and control mice were infected with Helicobacter felis to create a model of Helicobacter pylori infection--the most common human chronic infection.
resultsInfection with H. felis induced expression of Duox2 and Duoxa2 in the stomachs of wild-type mice, and DUOX protein specifically localized to the apical surface of epithelial cells. H. felis colonized the mucus layer in the stomachs of Duoxa(-/-) mice to a greater extent than in control mice. The increased colonization persisted into the chronic phase of infection and correlated with an increased, yet ineffective, inflammatory response. H. felis colonization also was increased in Duoxa(+/-) mice, compared with controls. We observed reduced expression of the H2O2-inducible katA gene in H. felis that colonized Duoxa(-/-) mice, compared with that found in controls (P = .0002), indicating that Duox causes oxidative stress in these bacteria. In vitro, induction of oxidative defense by H. felis failed to prevent a direct bacteriostatic effect at sustained levels of H2O2 as low as 30 μmol/L.
conclusionsBased on studies of Duoxa(-/-) mice, the DUOX enzyme complex prevents gastric colonization by H. felis and the inflammatory response. These findings indicate the nonredundant function of epithelial production of H2O2 in restricting microbial colonization.
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