ArticleInfection and immunity2009
Antibody-enhanced, Fc gamma receptor-mediated endocytosis of Clostridium difficile toxin A.
Article in Infection and immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 38 citations in OpenAlex.
- Low expression of FCGRIIB in macrophages of immune thrombocytopenia-affected individuals.International journal of hematology · 2012Trial
- Fit-for-purpose heterodivalent single-domain antibody for gastrointestinal targeting of toxin B from Clostridium difficile.Protein science : a publication of the Protein Society · 2024Article
- Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper.Nature communications · 2024Article
- Development of an Effective Nontoxigenic Clostridioides difficile-Based Oral Vaccine against C. difficile Infection.Microbiology spectrum · 2022Article
- Application of recombinant antibodies for treatment ofFrontiers in immunology · 2022Review
- Neutralizing epitopes onFrontiers in immunology · 2022Article
- Genetic engineering cellular vesicles expressing CD64 as checkpoint antibody carrier for cancer immunotherapy.Theranostics · 2021Article
- A probiotic yeast-based immunotherapy againstScience translational medicine · 2020Article
- Oral Immunization with Nontoxigenic Clostridium difficile Strains Expressing Chimeric Fragments of TcdA and TcdB Elicits Protective Immunity against C. difficile Infection in Both Mice and Hamsters.Infection and immunity · 2018Article
- Prospects from systems serology research.Immunology · 2018Review
- Beyond binding: antibody effector functions in infectious diseases.Nature reviews. Immunology · 2018Review
- Novel Chimeric Protein Vaccines AgainstFrontiers in immunology · 2018Article
- Intravenous adenovirus expressing a multi-specific, single-domain antibody neutralizing TcdA and TcdB protects mice from Clostridium difficile infection.Pathogens and disease · 2016Article
- Identification of an Essential Region for Translocation of Clostridium difficile Toxin B.Toxins · 2016Article
- An update on antibody-based immunotherapies for Clostridium difficile infection.Clinical and experimental gastroenterology · 2016Review
- Masking autoprocessing of Clostridium difficile toxin A by the C-terminus combined repetitive oligo peptides.Biochemical and biophysical research communications · 2015Article
- Clostridium difficile toxin B intoxicated mouse colonic epithelial CT26 cells stimulate the activation of dendritic cells.Pathogens and disease · 2015Article
- High temporal resolution of glucosyltransferase dependent and independent effects of Clostridium difficile toxins across multiple cell types.BMC microbiology · 2015Article
- Article
- A novel multivalent, single-domain antibody targeting TcdA and TcdB prevents fulminant Clostridium difficile infection in mice.The Journal of infectious diseases · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Toxin A (TcdA) and toxin B (TcdB) are major virulence factors of Clostridium difficile. These two toxins intoxicate cultured cells by similar mechanisms, and TcdB generally is more potent than TcdA in cultured cells. The exact reason for this difference is unclear. Here, we report that the cellular effects of TcdA can be substantially enhanced via an opsonizing antibody through Fc gamma receptor I (FcgammaRI)-mediated endocytosis. A TcdA-specific monoclonal antibody, A1H3, was found to significantly enhance the cytotoxicity of TcdA to macrophages and monocytes. The A1H3-dependent enhancement of glucosyltransferase activity, cytoskeleton disruption, and tumor necrosis factor alpha production induced by TcdA was further demonstrated using RAW 264.7 cells. Subsequent experiments indicated that the interaction of FcgammaRI with A1H3 underlays the antibody-dependent enhancement of the cellular effects of TcdA. While blocking FcgammaRII and FcgammaRIII with anti-CD16/32 antibodies did not affect the TcdA-mediated glucosylation of Rac1 in RAW 264.7 cells, presaturation of FcgammaRI with anti-CD64 antibodies in THP1 cells significantly reduced this activity. Incubation of a TcdA-A1H3 immune complex with recombinant mouse CD64 completely abrogated the A1H3-mediated enhancement of the glucosyltransferase activity of TcdA in RAW 264.7 cells. Moreover, expression of FcgammaRI in CHO cells strikingly enhanced the sensitivity of these cells to TcdA complexed with A1H3. We showed that the presence of A1H3 facilitated cell surface recruitment of TcdA, contributing to the antibody-dependent, FcgammaRI-mediated enhancement of TcdA activity. Finally, studies using chlorpromazine and endosomal acidification inhibitors revealed an important role of the endocytic pathway in the A1H3-dependent enhancement of TcdA activity.
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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.