ArticleThe EMBO journal2019
Antibody and DNA sensing pathways converge to activate the inflammasome during primary human macrophage infection.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Transcriptional transactivation turns human iPSC-derived macrophages into an adenovirus-producing cell state.Journal of virology · 2026Article
- Adenovirus phagocytosis by neutrophils triggers a pro-inflammatory response.PLoS pathogens · 2026Article
- Review
- cGAS-STING-NF-κB Axis Mediates Rotenone-Induced NLRP3 Inflammasome Activation Through Mitochondrial DNA Release.Antioxidants (Basel, Switzerland) · 2025Article
- Pyroptosis in Respiratory Virus Infections: A Narrative Review of Mechanisms, Pathophysiology, and Potential Therapeutic Interventions.Microorganisms · 2025Review
- Mechanisms of antibody-dependent enhancement of infectious disease.Nature reviews. Immunology · 2025Review
- TRIM32 reduced the recruitment of innate immune cells and the killing capacity of Listeria monocytogenes by inhibiting secretion of chemokines.Gut pathogens · 2023Article
- Review
- Multiple Roles of TRIM21 in Virus Infection.International journal of molecular sciences · 2023Review
- Functional skewing of TRIM21-SIRT5 interplay dictates IL-1β production in DSS-induced colitis.EMBO reports · 2022Article
- Potent TRIM21 and complement-dependent intracellular antiviral immunity requires the IgG3 hinge.Science immunology · 2022Article
- Leveraging Antibody, B Cell and Fc Receptor Interactions to Understand Heterogeneous Immune Responses in Tuberculosis.Frontiers in immunology · 2022Review
- A viral ubiquitination switch attenuates innate immunity and triggers nuclear import of virion DNA and infection.Science advances · 2021Article
- Potential Diagnostic and Prognostic Biomarkers for Adenovirus Respiratory Infection in Children and Young Adults.Viruses · 2021Review
- TRIM Proteins in Inflammation: from Expression to Emerging Regulatory Mechanisms.Inflammation · 2021Review
- Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity.The EMBO journal · 2021Article
- Immune Response against Adenovirus in Acute Upper Respiratory Tract Infections in Immunocompetent Children.Vaccines · 2020Article
- "Repair Me if You Can": Membrane Damage, Response, and Control from the Viral Perspective.Cells · 2020Review
- Intracellular antibody immunity and its applications.PLoS pathogens · 2020Article
- NLRP3 inflammasome activation by Foot-and-mouth disease virus infection mainly induced by viral RNA and non-structural protein 2B.RNA biology · 2020Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Inflammasomes are potent innate immune signalling complexes that couple cytokine release with pro-inflammatory cell death. However, pathogens have evolved strategies to evade this cell autonomous system. Here, we show how antibodies combine with innate sensors in primary human macrophages to detect viral infection and activate the inflammasome. Our data demonstrate that antibody opsonisation of virions can activate macrophages in multiple ways. In the first, antibody binding of adenovirus causes lysosomal damage, activating NLRP3 to drive inflammasome formation and IL-1β release. Importantly, this mechanism enhances virion capture but not infection and is accompanied by cell death, denying the opportunity for viral replication. Unexpectedly, we also find that antibody-coated viruses, which successfully escape into the cytosol, trigger a second system of inflammasome activation. These viruses are intercepted by the cytosolic antibody receptor TRIM21 and the DNA sensor cGAS. Together, these sensors stimulate both NLRP3 inflammasome formation and NFκB activation, driving dose-dependent IL-1β and TNF secretion, without inducing cell death. Our data highlight the importance of cooperativity between multiple sensing networks to expose viruses to the inflammasome pathway, which is particularly important for how our innate immune system responds to infection in the presence of pre-existing immunity.
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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.