ArticlePLoS pathogens2013
IL-1β production through the NLRP3 inflammasome by hepatic macrophages links hepatitis C virus infection with liver inflammation and disease.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 255 papers, 2 of them syntheses that pooled it.
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Who cites it
255 citing papers in PubMed, 2 syntheses or guidelines pooled it, 407 citations in OpenAlex.
- Advances in NLRP3 inflammasome research in viral infections: evolution, trends, and future directions.Frontiers in cellular and infection microbiology · 2026Pooled it
- Inflammasomes and their roles in the pathogenesis of viral hepatitis and their related complications: An updated systematic review.Immunology letters · 2019Pooled it
- Liver Macrophages in the Pathogenesis of Viral Hepatitis.Current issues in molecular biology · 2026Review
- Risk Factors and Biomarkers for Immune Checkpoint Inhibitor-mediated Hepatotoxicity: Emerging Insights and Future Perspectives.Journal of clinical and translational hepatology · 2026Review
- Targeting pattern recognition receptors for cancer therapy: Mechanisms and strategies.Acta pharmaceutica Sinica. B · 2025Review
- ANXA2 in hepatocellular carcinoma: orchestrating tumorigenesis, progression, and therapeutic resistance toward precision targeting.Journal of translational medicine · 2025Review
- Inflammasomes and autophagy in cancer: unlocking targeted therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Expression of intron-containing HIV-1 RNA induces NLRP1 inflammasome activation in myeloid cells.PLoS biology · 2025Article
- Targeted degradation of GSPT1 and NEK7 by a molecular glue prodrug for treatment of HCC.Communications chemistry · 2025Article
- A historical perspective of Kupffer cells in the context of infection.Cell and tissue research · 2025Review
- Impact of NSAIDs corticosteroids DMARDs biologics and their comparisons with natural products in C-reactive proteins (CRP) linked cardiovascular disorders.Inflammopharmacology · 2025Review
- LPS-Induced Liver Inflammation Is Inhibited by Psilocybin and Eugenol in Mice.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Clusterin deficiency exacerbates cholestatic liver disease through ER stress and NLRP3 inflammasome activation.Cell & bioscience · 2025Article
- Activation and evasion of inflammasomes during viral and microbial infection.Cellular and molecular life sciences : CMLS · 2025Review
- NLRP3 Inflammasome Activation in Liver Disorders: From Molecular Pathways to Therapeutic Strategies.Journal of inflammation research · 2025Review
- Innate immune role of IL-6 in influenza a virus pathogenesis.Frontiers in cellular and infection microbiology · 2025Review
- The inflammasome next door: characterizing pyroptosis induction in HCV-infected and uninfected bystander cellsFrontiers in cellular and infection microbiology · 2025Article
- Functional Role of Hepatitis C Virus NS5A in the Regulation of Autophagy.Pathogens (Basel, Switzerland) · 2024Review
- Review
- NLRP3 inflammasome inhibition decreasesInfection and immunity · 2024Article
195 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease. Liver inflammation underlies infection-induced fibrosis, cirrhosis and liver cancer but the processes that promote hepatic inflammation by HCV are not defined. We provide a systems biology analysis with multiple lines of evidence to indicate that interleukin-1β (IL-1β) production by intrahepatic macrophages confers liver inflammation through HCV-induced inflammasome signaling. Chronic hepatitis C patients exhibited elevated levels of serum IL-1β compared to healthy controls. Immunohistochemical analysis of healthy control and chronic hepatitis C liver sections revealed that Kupffer cells, resident hepatic macrophages, are the primary cellular source of hepatic IL-1β during HCV infection. Accordingly, we found that both blood monocyte-derived primary human macrophages, and Kupffer cells recovered from normal donor liver, produce IL-1β after HCV exposure. Using the THP-1 macrophage cell-culture model, we found that HCV drives a rapid but transient caspase-1 activation to stimulate IL-1β secretion. HCV can enter macrophages through non-CD81 mediated phagocytic uptake that is independent of productive infection. Viral RNA triggers MyD88-mediated TLR7 signaling to induce IL-1β mRNA expression. HCV uptake concomitantly induces a potassium efflux that activates the NLRP3 inflammasome for IL-1β processing and secretion. RNA sequencing analysis comparing THP1 cells and chronic hepatitis C patient liver demonstrates that viral engagement of the NLRP3 inflammasome stimulates IL-1β production to drive proinflammatory cytokine, chemokine, and immune-regulatory gene expression networks linked with HCV disease severity. These studies identify intrahepatic IL-1β production as a central feature of liver inflammation during HCV infection. Thus, strategies to suppress NLRP3 or IL-1β activity could offer therapeutic actions to reduce hepatic inflammation and mitigate disease.
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Registered trials
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.