ArticleProceedings of the National Academy of Sciences of the United States of America2014
IRAK-1 bypasses priming and directly links TLRs to rapid NLRP3 inflammasome activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 160 papers.
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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.
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Who cites it
160 citing papers in PubMed, 282 citations in OpenAlex.
- The Role of Skeletal Muscle Mitochondria in NLRP3 Inflammasome Signaling.Biomolecules · 2026Review
- Infectious bronchitis virus accessory protein 3a induces renal inflammatory injury by activating the NLRP3 inflammasome via ER calcium mobilization and mitochondrial ROS production.Journal of virology · 2026Article
- LTBP4 deficiency inhibits NLRP3 inflammasome activation in cardiomyocytes and attenuates heart failure in male mice.Nature communications · 2026Article
- Post-translational modifications of NLRP3: to prime or not to prime?Trends in immunology · 2026Review
- Article
- The role of NLRP3 inflammasome in age-related macular degeneration: mechanisms and therapeutic prospects.Frontiers in aging neuroscience · 2026Review
- NLRP3 inflammasome in acute kidney injury: molecular mechanisms, post-translational regulation, and immunotherapeutic potential.Frontiers in immunology · 2026Review
- Molecular Insights and Therapeutic Advances in Low-Risk Myelodysplastic Neoplasms: A Clinical Review.Cancers · 2025Review
- Genetic removal of Nlrp3 protects against age-related and R345W Efemp1-induced basal laminar deposit formation.Cell death & disease · 2025Article
- IRAK signaling in cancers: mechanisms, targeting, and clinical implications.Expert opinion on investigational drugs · 2025Review
- Pattern recognition receptors: function, regulation and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- Clustering of NLRP3 induced by membrane or protein scaffolds promotes inflammasome assembly.Nature communications · 2025Article
- Innate immune mechanisms of infection: what we know and potential conserved mechanisms affecting sleep during infection.Neurobiology of sleep and circadian rhythms · 2025Article
- Allopurinol abates hepatocellular carcinoma in rats via modulation of NLRP3 inflammasome and NF-κB pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Modeling Necroptotic and Pyroptotic Signaling inBiomolecules · 2025Review
- TBK1 and IKKε prevent premature cell death by limiting the activity of both RIPK1 and NLRP3 death pathways.Science advances · 2025Article
- Cornuside alleviates cognitive impairments induced by AβAlzheimer's research & therapy · 2025Article
- Mechanistic insights from inflammasome structures.Nature reviews. Immunology · 2024Review
- Role of NLRP3 inflammasome in central nervous system diseases.Cell & bioscience · 2024Review
- Post-translational control of NLRP3 inflammasome signaling.The Journal of biological chemistry · 2024Review
100 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Pathogenic infections and tissue injuries trigger the assembly of inflammasomes, cytosolic protein complexes that activate caspase-1, leading to cleavage of pro-IL-1β and pro-IL-18 and to pyroptosis, a proinflammatory cell death program. Although microbial recognition by Toll-like receptors (TLRs) is known to induce the synthesis of the major caspase-1 substrate pro-IL-1β, the role of TLRs has been considered limited to up-regulation of the inflammasome components. During infection with a virulent microbe, TLRs and nucleotide-binding oligomerization domain-like receptors (NLRs) are likely activated simultaneously. To examine the requirements and outcomes of combined activation, we stimulated TLRs and a specific NLR, nucleotide binding and oligomerization, leucine-rich repeat, pyrin domain-containing 3 (NLRP3), simultaneously and discovered that such activation triggers rapid caspase-1 cleavage, leading to secretion of presynthesized inflammatory molecules and pyroptosis. This acute caspase-1 activation is independent of new protein synthesis and depends on the TLR-signaling molecule IL-1 receptor-associated kinase (IRAK-1) and its kinase activity. Importantly, Listeria monocytogenes induces NLRP3-dependent rapid caspase-1 activation and pyroptosis, both of which are compromised in IRAK-1-deficient macrophages. Our results reveal that simultaneous sensing of microbial ligands and virulence factors by TLRs and NLRP3, respectively, leads to a rapid TLR- and IRAK-1-dependent assembly of the NLRP3 inflammasome complex, and that such activation is important for release of alarmins, pyroptosis, and early IFN-γ production by memory CD8 T cells, all of which could be critical for early host defense.
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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.