ArticlePLoS pathogens2014
The inflammasome pyrin contributes to pertussis toxin-induced IL-1β synthesis, neutrophil intravascular crawling and autoimmune encephalomyelitis.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Role of Inflammasomes in Neuroimmune and Neurodegenerative Diseases: A Systematic Review.Mediators of inflammation · 2018Pooled it
- DCIR-mediated inhibitory regulation of TLR7-MyD88 axis prevents autoimmune neuroinflammation.iScience · 2026Article
- Advancing EAE Modeling: Establishment of a Non-Pertussis Immunization Protocol for Multiple Sclerosis.Bio-protocol · 2026Article
- Pattern recognition receptors and inflammasome: Now and beyond.Molecules and cells · 2025Review
- Inflammatory Responses Potentiate GAS M Protein Induced Cardiac Damage in an Experimental Model of Rheumatic Heart Disease.Immunity, inflammation and disease · 2025Article
- Activation and evasion of inflammasomes during viral and microbial infection.Cellular and molecular life sciences : CMLS · 2025Review
- A Defined Diet Combined with Sonicated Inoculum Provides a High Incidence, Moderate Severity Form of Experimental Autoimmune Encephalomyelitis (EAE).ACS pharmacology & translational science · 2024Article
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- Neutrophil extracellular traps are involved in the occurrence of interstitial lung disease in a murine experimental autoimmune myositis model.Clinical and experimental immunology · 2024Article
- Pyroptosis the Emerging Link Between Gut Microbiota and Multiple Sclerosis.Drug design, development and therapy · 2024Review
- Extracellular vesicles mediate inflammasome signaling in the brain and heart of Alzheimer's disease mice.Frontiers in molecular neuroscience · 2024Article
- Article
- Neural-Cardiac Inflammasome Axis after Traumatic Brain Injury.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Atranorin inhibits NLRP3 inflammasome activation by targeting ASC and protects NLRP3 inflammasome-driven diseases.Acta pharmacologica Sinica · 2023Article
- The C-type lectin receptor Clec1A plays an important role in the development of experimental autoimmune encephalomyelitis by enhancing antigen presenting ability of dendritic cells and inducing inflammatory cytokine IL-17.Experimental animals · 2022Article
- Potential role of BAY11-7082, a NF-κB blocker inhibiting experimental autoimmune encephalomyelitis in C57BL/6J mice via declining NLRP3 inflammasomes.Clinical and experimental immunology · 2022Article
- Article
- Focus on the Role of the NLRP3 Inflammasome in Multiple Sclerosis: Pathogenesis, Diagnosis, and Therapeutics.Frontiers in molecular neuroscience · 2022Review
- Phenotypical and Functional Characterization of Neutrophils in Two Pyrin-Associated Auto-inflammatory Diseases.Journal of clinical immunology · 2021Article
- Pertussis Toxin Inhibits Encephalitogenic T-Cell Infiltration and Promotes a B-Cell-Driven Disease during Th17-EAE.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microbial agents can aggravate inflammatory diseases, such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). An example is pertussis toxin (PTX), a bacterial virulence factor commonly used as an adjuvant to promote EAE, but whose mechanism of action is unclear. We have reported that PTX triggers an IL-6-mediated signaling cascade that increases the number of leukocytes that patrol the vasculature by crawling on its luminal surface. In the present study, we examined this response in mice lacking either TLR4 or inflammasome components and using enzymatically active and inactive forms of PTX. Our results indicate that PTX, through its ADP-ribosyltransferase activity, induces two series of events upstream of IL-6: 1) the activation of TLR4 signaling in myeloid cells, leading to pro-IL-1β synthesis; and 2) the formation of a pyrin-dependent inflammasome that cleaves pro-IL-1β into its active form. In turn, IL-1β stimulates nearby stromal cells to secrete IL-6, which is known to induce vascular changes required for leukocyte adhesion. Without pyrin, PTX does not induce neutrophil adhesion to cerebral capillaries and is less effective at inducing EAE in transgenic mice with encephalitogenic T lymphocytes. This study identifies the first microbial molecule that activates pyrin, a mechanism by which infections may influence MS and a potential therapeutic target for immune disorders.
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