ArticleInfection and immunity2004
Intact gram-negative Helicobacter pylori, Helicobacter felis, and Helicobacter hepaticus bacteria activate innate immunity via toll-like receptor 2 but not toll-like receptor 4.
Article in Infection and immunity, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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.
The trial behind it
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
89 citing papers in PubMed, 226 citations in OpenAlex.
- Article
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- Dominant effects of the immediate environment on the gut microbiome of mice used in biomedical research.mSystems · 2025Article
- Akkermansia muciniphila: biology, microbial ecology, host interactions and therapeutic potential.Nature reviews. Microbiology · 2025Review
- Nobiletin restores the intestinal barrier of HFD-induced obese mice by promoting MHC-II expression and lipid metabolism.Molecular medicine (Cambridge, Mass.) · 2025Article
- Toll-like Receptor 4 Signaling Mediates Gastritis and Gastric Cancer.Current molecular medicine · 2025Review
- Comparison of gastric inflammation and metaplasia induced byMicrobiology spectrum · 2024Article
- The immunopathogenesis ofFrontiers in microbiology · 2024Review
- Immune evasion by proteolytic shedding of natural killer group 2, member D ligands inFrontiers in immunology · 2024Article
- Porphyromonas gingivalis Lipopolysaccharide Damages Mucosal Barrier to Promote Gastritis-Associated Carcinogenesis.Digestive diseases and sciences · 2024Article
- Essential role ofInfection and immunity · 2023Article
- Heterogeneity of Lipopolysaccharide as Source of Variability in Bioassays and LPS-Binding Proteins as Remedy.International journal of molecular sciences · 2023Review
- Lipopolysaccharide detection by the innate immune system may be an uncommon defence strategy used in nature.Open biology · 2022Review
- Helicobacter pylori Infection Elicits Type I Interferon Response in Human Monocytes via Toll-Like Receptor 8 Signaling.Journal of immunology research · 2022Article
- Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis.Cell stem cell · 2021Article
- Ruminal Lipopolysaccharides Analysis: Uncharted Waters with Promising Signs.Animals : an open access journal from MDPI · 2021Review
- Contribution of Heptose Metabolites and theFrontiers in immunology · 2021Article
- Innate Memory Reprogramming by Gold Nanoparticles Depends on the Microbial Agents That Induce Memory.Frontiers in immunology · 2021Article
- An Overview of Helicobacter pylori Infection.Methods in molecular biology (Clifton, N.J.) · 2021Review
29 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
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Molecular and genetic studies have demonstrated that members of the Toll-like receptor (TLR) family are critical innate immune receptors. TLRs are recognition receptors for a diverse group of microbial ligands including bacteria, fungi, and viruses. This study demonstrates that distinct TLRs are responsible for the recognition of Helicobacter lipopolysaccharide (LPS) versus intact Helicobacter bacteria. We show that the cytokine-inducing activity of Helicobacter LPS was mediated by TLR4; i.e., TLR4-deficient macrophages were unresponsive to Helicobacter pylori LPS. Surprisingly, the cytokine response to whole Helicobacter bacteria (H. pylori, H. hepaticus, and H. felis) was mediated not by TLR4 but rather by TLR2. Studies of HEK293 transfectants revealed that expression of human TLR2 was sufficient to confer responsiveness to intact Helicobacter bacteria, but TLR4 transfection was not sufficient. Our studies further suggest that cag pathogenicity island genes may modulate the TLR2 agonist activity of H. pylori as cagA+ bacteria were more active on a per-cell basis compared to cagA mutant bacteria for interleukin-8 (IL-8) cytokine secretion. Consistent with the transfection studies, analysis of knockout mice demonstrated that TLR2 was required for the cytokine response to intact Helicobacter bacteria. Macrophages from both wild-type and TLR4-deficient mice produced a robust cytokine secretion response (IL-6 and MCP-1) when stimulated with intact Helicobacter bacteria. In contrast, macrophages from TLR2-deficient mice were profoundly unresponsive to intact Helicobacter stimulation, failing to secrete cytokines even at high (100:1) bacterium-to-macrophage ratios. Our studies suggest that TLR2 may be the dominant innate immune receptor for recognition of gastrointestinal Helicobacter species.
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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.