ArticleMicrobial pathogenesis2009
Essential role of the glucosyltransferase activity in Clostridium difficile toxin-induced secretion of TNF-alpha by macrophages.
Article in Microbial pathogenesis, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Clostridioides difficile : A suspected pro-carcinogenic bacterium for gastrointestinal tumors.Chinese medical journal · 2026Review
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- Textile azo dye, Sudan Black B, inducing hepatotoxicity demonstrated in in vivo zebrafish larval model.Fish physiology and biochemistry · 2024Article
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
- The effect of differentHeliyon · 2023Article
- Large Clostridial Toxins: Mechanisms and Roles in Disease.Microbiology and molecular biology reviews : MMBR · 2021Review
- Article
- Enterotoxic Clostridia:Microbiology spectrum · 2019Review
- Tumour Necrosis Factor Alpha in Intestinal Homeostasis and Gut Related Diseases.International journal of molecular sciences · 2019Review
- TNF/TNFR axis promotes pyrin inflammasome activation and distinctly modulates pyrin inflammasomopathy.The Journal of clinical investigation · 2019Article
- TPL2 Is a Key Regulator of Intestinal Inflammation in Clostridium difficile Infection.Infection and immunity · 2018Article
- On and Off: A Dual Role for Cysteine Protease Autoprocessing ofCellular and molecular gastroenterology and hepatology · 2018Article
- The role of toxins in Clostridium difficile infection.FEMS microbiology reviews · 2017Review
- Glucosylation Drives the Innate Inflammatory Response to Clostridium difficile Toxin A.Infection and immunity · 2016Article
- Pathogenic effects of glucosyltransferase from Clostridium difficile toxins.Pathogens and disease · 2016Review
- Analysis of TcdB Proteins within the Hypervirulent Clade 2 Reveals an Impact of RhoA Glucosylation on Clostridium difficile Proinflammatory Activities.Infection and immunity · 2016Article
- Review
- Review
- Clostridium difficile toxin B intoxicated mouse colonic epithelial CT26 cells stimulate the activation of dendritic cells.Pathogens and disease · 2015Article
- The role of Gr-1(+) cells and tumour necrosis factor-α signalling during Clostridium difficile colitis in mice.Immunology · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Clostridium difficile causes serious and potentially fatal inflammatory diseases of the colon. Two large protein toxins, TcdA and TcdB, have been clearly implicated in pathogenesis. The goal of this study was to determine whether the glucosyltransferase activity of the toxins is critical for the induction of tumor necrosis factor-alpha (TNF-alpha), an important cytokine mediating both local and systematic inflammatory response. A dose-dependent TNF-alpha secretion was demonstrated in murine macrophage cell line RAW 264.7 after exposure to TcdA or TcdB. TNF-alpha production was blocked by anti-toxin antibodies, indicating that the cytokine-driven response is mediated by the toxins. Both toxins disrupted the cytoskeleton of host cells, while cytoskeleton disruptions using Cytochalasin-D and latrunculin B did not affect TNF-alpha production. The TNF-alpha synthesis was inhibited by reagents that target clathrin-dependent endocytosis or prevent endosomal acidification, suggesting that the endocytosis pathway is necessary for the induction of TNF-alpha. Furthermore, knockout of the enzymatic activity by mutating two key amino acids in the catalytic domain of TcdA abolished its cytokine-inducing activity. Our studies demonstrated a crucial role of the glucosyltransferase activity of C. difficile toxins in the induction of TNF-alpha in macrophages.
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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.