ArticleProceedings of the National Academy of Sciences of the United States of America2018
Digital signaling network drives the assembly of the AIM2-ASC inflammasome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- RETRACTED: Endogenous Retroviruses as Regulators of Innate Immune Signaling and InflammationViruses · 2026Review
- Structural insights into the atypical filament assembly of pyrin domain-containing IFI16.The EMBO journal · 2025Article
- Self-DNA by Activating the CGAS-STING1 Pathway Contributes to the Pathogenesis of Atherosclerosis.Current atherosclerosis reports · 2025Review
- Transient Poly(ADP-Ribose) Triggers FUS Condensation Hysteresis via a Prion-Like Mechanism.bioRxiv : the preprint server for biology · 2025Article
- Activation and evasion of inflammasomes during viral and microbial infection.Cellular and molecular life sciences : CMLS · 2025Review
- DNA sensors in metabolic and cardiovascular diseases: Molecular mechanisms and therapeutic prospects.Immunological reviews · 2025Review
- Cytosolic DNA sensors in neurodegenerative diseases: from physiological defenders to pathological culprits.EMBO molecular medicine · 2024Review
- Article
- The impact of AIM2 inflammasome-induced pyroptosis on acute gouty arthritis and asymptomatic hyperuricemia patients.Frontiers in immunology · 2024Article
- Inflammasomes and idiopathic inflammatory myopathies.Frontiers in immunology · 2024Review
- The roles of AIM2 in neurodegenerative diseases: insights and therapeutic implications.Frontiers in immunology · 2024Review
- Assembly mechanism of the inflammasome sensor AIM2 revealed by single molecule analysis.Nature communications · 2023Article
- Inhibition of AIM2 inflammasome activation by SOX/ORF37 promotes lytic replication of Kaposi's sarcoma-associated herpesvirus.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Oligomeric states of ASC specks regulate inflammatory responses by inflammasome in the extracellular space.Cell death discovery · 2023Article
- Filament assembly underpins the double-stranded DNA specificity of AIM2-like receptors.Nucleic acids research · 2023Article
- Endogenous Retroviruses as Modulators of Innate Immunity.Pathogens (Basel, Switzerland) · 2023Review
- Nanomaterial-induced pyroptosis: a cell type-specific perspective.Frontiers in cell and developmental biology · 2023Review
- Role of the inflammasome in insulin resistance and type 2 diabetes mellitus.Frontiers in immunology · 2023Review
- Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors.Biomedicines · 2022Review
- Article
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The AIM2-ASC inflammasome is a filamentous signaling platform essential for mounting host defense against cytoplasmic dsDNA arising not only from invading pathogens but also from damaged organelles. Currently, the design principles of its underlying signaling network remain poorly understood at the molecular level. We show here that longer dsDNA is more effective in inducing AIM2 assembly, its self-propagation, and downstream ASC polymerization. This observation is related to the increased probability of forming the base of AIM2 filaments, and indicates that the assembly discerns small dsDNA as noise at each signaling step. Filaments assembled by receptor AIM2, downstream ASC, and their joint complex all persist regardless of dsDNA, consequently generating sustained signal amplification and hysteresis. Furthermore, multiple positive feedback loops reinforce the assembly, as AIM2 and ASC filaments accelerate the assembly of nascent AIM2 with or without dsDNA. Together with a quantitative model of the assembly, our results indicate that an ultrasensitive digital circuit drives the assembly of the AIM2-ASC inflammasome.
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