ArticleInfection and immunity2015
Aggregatibacter actinomycetemcomitans cytolethal distending toxin activates the NLRP3 inflammasome in human macrophages, leading to the release of proinflammatory cytokines.
Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed.
- Associations Between Neuromuscular Fatigue, Anxiety, and Peripheral Biomarkers of Neuronal Injury, Inflammation, and Mitochondrial Dysfunction in Treatment-Naïve Relapsing-Remitting Multiple Sclerosis.Brain and behavior · 2026Article
- The Role of Lacticaseibacillus Rhamnosus in Periodontitis Management: From Microecological Regulation to Clinical Application.Probiotics and antimicrobial proteins · 2026Review
- Folate receptor beta drives NLRP3 inflammasome activation and pyroptosis in macrophages independent of folate binding.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Review
- Effect of nonsurgical periodontal treatment on NLRP3, Nrf2, Caspase-1, interleukin-1B, interleukin-18 in gingival crevicular fluid of severe periodontitis.Clinical oral investigations · 2025Article
- The Periodontal-Cardiovascular Disease Association: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2025Review
- Cytolethal distending toxin from Glaesserella parasuis induces ferroptosis in porcine alveolar macrophages and mice.Veterinary research · 2025Article
- Caspase-11 mediated inflammasome activation in macrophages by systemic infection of A. actinomycetemcomitans exacerbates arthritis.International journal of oral science · 2024Article
- Dying for a cause: The pathogenic manipulation of cell death and efferocytic pathways.Molecular oral microbiology · 2024Review
- Recent Aspects of Periodontitis and Alzheimer's Disease-A Narrative Review.International journal of molecular sciences · 2024Review
- Article
- The Roles of Periodontal Bacteria in Atherosclerosis.International journal of molecular sciences · 2023Review
- Macrophages in periodontitis: A dynamic shift between tissue destruction and repair.The Japanese dental science review · 2022Review
- Activation and Function of NLRP3 Inflammasome in Bone and Joint-Related Diseases.International journal of molecular sciences · 2022Review
- Advances in the Study of Bacterial Toxins, Their Roles and Mechanisms in Pathogenesis.The Malaysian journal of medical sciences : MJMS · 2022Review
- Nrf2 in the Field of Dentistry with Special Attention to NLRP3.Antioxidants (Basel, Switzerland) · 2022Review
- Lactobacilli Attenuate the Effect ofFrontiers in microbiology · 2022Article
- Focus on the Role of the NLRP3 Inflammasome in Multiple Sclerosis: Pathogenesis, Diagnosis, and Therapeutics.Frontiers in molecular neuroscience · 2022Review
- Bacterial Toxins Are a Never-Ending Source of Surprises: From Natural Born Killers to Negotiators.Toxins · 2021Review
- Associations of Antibodies Targeting Periodontal Pathogens With Subclinical Coronary, Carotid, and Peripheral Arterial Atherosclerosis in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The cytolethal distending toxin (Cdt) is produced from a number of bacteria capable of causing infection and inflammatory disease. Our previous studies with Actinobacillus actinomycetemcomitans Cdt demonstrate not only that the active toxin subunit functions as a phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase but also that macrophages exposed to the toxin were stimulated to produce proinflammatory cytokines. We now demonstrate that the Cdt-induced proinflammatory response involves the activation of the NLRP3 inflammasome. Specific inhibitors and short hairpin RNA (shRNA) were employed to demonstrate requirements for NLRP3 and ASC as well as caspase-1. Furthermore, Cdt-mediated inflammasome activation is dependent upon upstream signals, including reactive oxygen species (ROS) generation and Cdt-induced increases in extracellular ATP levels. Increases in extracellular ATP levels contribute to the activation of the P2X7 purinergic receptor, leading to K+ efflux. The relationship between the abilities of the active toxin subunit CdtB to function as a lipid phosphatase, activate the NLRP3 inflammasome, and induce a proinflammatory cytokine response is discussed. These studies provide new insight into the virulence potential of Cdt in mediating the pathogenesis of disease caused by Cdt-producing organisms such as Aggregatibacter actinomycetemcomitans.
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