ArticlePLoS pathogens2021
The ALPK1 pathway drives the inflammatory response to Campylobacter jejuni in human intestinal epithelial cells.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Determinate the effects of Arabic gum and Lactobacillus acidophilus on the gut microbiota ALPK1/NFKB/NLRP6 and NLRP2 signaling pathway and virulence gene profile in rats with Campylobacter jejuni exosome application.Archives of microbiology · 2026Article
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- Investigating the role of the ALPK1 signaling pathway in the pathogenesis of diabetic retinopathy.Scientific reports · 2025Article
- Discovery of a selective alpha-kinase 1 inhibitor for the rare genetic disease ROSAH syndrome.Nature communications · 2025Article
- Targeting TNFAIP2 with NIR-II CRISPR-Cas9 nanosystem to overcome cisplatin resistance in laryngeal cancer.NPJ precision oncology · 2025Article
- The importance of ALPK1 kinase functionality as a potential biomarker for inflammatory diseases.Molecular biology reports · 2025Review
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- Actinobacteria: Smart Micro-Factories for The Health Sector.Recent patents on biotechnology · 2025Review
- Campylobacter jejuni virulence factors: update on emerging issues and trends.Journal of biomedical science · 2024Review
- The relationship of ALPK1, hyaluronic acid and M1 macrophage polarization in the temporomandibular joint synovitis.Journal of cellular and molecular medicine · 2024Article
- Characterization of the ADP-β-D-manno-heptose biosynthetic enzymes from two pathogenic Vibrio strains.Applied microbiology and biotechnology · 2024Article
- Copper regulates the host innate immune response against bacterial infection via activation of ALPK1 kinase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Helicobacter pylori Modulates Heptose Metabolite Biosynthesis and Heptose-Dependent Innate Immune Host Cell Activation by Multiple Mechanisms.Microbiology spectrum · 2023Article
- A Bittersweet Kiss of Gram-Negative Bacteria: The Role of ADP-Heptose in the Pathogenesis of Infection.Microorganisms · 2023Review
- Campylobacter jejuni: targeting host cells, adhesion, invasion, and survival.Applied microbiology and biotechnology · 2023Review
- The Role of Microbiota-Derived Metabolites in Colorectal Cancer.International journal of molecular sciences · 2023Review
- In vitro kinase assay reveals ADP-heptose-dependent ALPK1 autophosphorylation and altered kinase activity of disease-associated ALPK1 mutants.Scientific reports · 2023Article
- Gain-of-function mutations inAnnals of the rheumatic diseases · 2022Article
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Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Gram-negative bacterium Campylobacter jejuni is a major cause of foodborne disease in humans. After infection, C. jejuni rapidly colonizes the mucus layer of the small and large intestine and induces a potent pro-inflammatory response characterized by the production of a large repertoire of cytokines, chemokines, and innate effector molecules, resulting in (bloody) diarrhea. The virulence mechanisms by which C. jejuni causes this intestinal response are still largely unknown. Here we show that C. jejuni releases a potent pro-inflammatory compound into its environment, which activates an NF-κB-mediated pro-inflammatory response including the induction of CXCL8, CXCL2, TNFAIP2 and PTGS2. This response was dependent on a functional ALPK1 receptor and independent of Toll-like Receptor and Nod-like Receptor signaling. Chemical characterization, inactivation of the heptose-biosynthesis pathway by the deletion of the hldE gene and in vitro engineering identified the released factor as the LOS-intermediate ADP-heptose and/or related heptose phosphates. During C. jejuni infection of intestinal cells, the ALPK1-NF-κB axis was potently activated by released heptose metabolites without the need for a type III or type IV injection machinery. Our results classify ADP-heptose and/or related heptose phosphates as a major virulence factor of C. jejuni that may play an important role during Campylobacter infection in humans.
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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.