ArticlePLoS pathogens2019
Nlrp3 inflammasome activation and Gasdermin D-driven pyroptosis are immunopathogenic upon gastrointestinal norovirus infection.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 94 citations in OpenAlex.
- Review
- The challenge of cell death switching in inflammasome-targeted therapies for bacterial and viral infections.Communications biology · 2026Review
- Podocyte-specific acid sphingomyelinase overexpression promotes gasdermin D dependent pyroptosis by impairing autophagic flux during obesity.Frontiers in physiology · 2026Article
- Mechanistic insights into gasdermin-mediated pyroptosis.Nature reviews. Molecular cell biology · 2025Review
- Egress-enhancing mutation reveals the inefficiency of non-enveloped virus cell exit.PLoS biology · 2025Article
- Pyroptosis: molecular mechanisms and roles in disease.Cell research · 2025Review
- Norovirus co-opts NINJ1 for selective protein secretion.Science advances · 2025Article
- Group B Streptococcal Membrane Vesicles Induce Proinflammatory Cytokine Production and Are Sensed in an NLRP3 Inflammasome-Dependent Mechanism in a Human Macrophage-like Cell Line.ACS infectious diseases · 2025Article
- TREM-1 as a Potential Coreceptor in Norovirus Pathogenesis: Insights from Transcriptomic Analysis and Molecular Docking.ACS omega · 2025Article
- The role of protein S-acylation in vascular injury associated with metabolic disorders.Frontiers in endocrinology · 2025Review
- To die or not to die: Gasdermins in intestinal health and disease.Seminars in immunology · 2024Review
- Ibuprofen inhibits anaplastic thyroid cells in vivo and in vitro by triggering NLRP3-ASC-GSDMD-dependent pyroptosis.Inflammopharmacology · 2024Article
- Knockdown of LCN2 Attenuates Brain Injury After Intracerebral Hemorrhage via Suppressing Pyroptosis.Neuropsychiatric disease and treatment · 2024Article
- Reduced hydrogen sulfide production contributes to adrenal insufficiency induced by hypoxia via modulation of NLRP3 inflammasome activation.Redox report : communications in free radical research · 2023Article
- The gasdermin protein family: emerging roles in gastrointestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2023Review
- Article
- Lipocalin-2 Deficiency Diminishes Canonical NLRP3 Inflammasome Formation and IL-1β Production in the Subacute Phase of Spinal Cord Injury.International journal of molecular sciences · 2023Article
- Article
- Jatrorrhizine Suppresses Murine-Norovirus-Triggered N-GSDMD-Dependent Pyroptosis in RAW264.7 Macrophages.Vaccines · 2023Article
- Cell death proteins in sepsis: key players and modern therapeutic approaches.Frontiers in immunology · 2023Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Norovirus infection is the leading cause of food-borne gastroenteritis worldwide, being responsible for over 200,000 deaths annually. Studies with murine norovirus (MNV) showed that protective STAT1 signaling controls viral replication and pathogenesis, but the immune mechanisms that noroviruses exploit to induce pathology are elusive. Here, we show that gastrointestinal MNV infection leads to widespread IL-1β maturation in MNV-susceptible STAT1-deficient mice. MNV activates the canonical Nlrp3 inflammasome in macrophages, leading to maturation of IL-1β and to Gasdermin D (GSDMD)-dependent pyroptosis. STAT1-deficient macrophages displayed increased MAVS-mediated expression of pro-IL-1β, facilitating elevated Nlrp3-dependent release of mature IL-1β upon MNV infection. Accordingly, MNV-infected Stat1-/- mice showed Nlrp3-dependent maturation of IL-1β as well as Nlrp3-dependent pyroptosis as assessed by in vivo cleavage of GSDMD to its active N-terminal fragment. While MNV-induced diarrheic responses were not affected, Stat1-/- mice additionally lacking either Nlrp3 or GSDMD displayed lower levels of the fecal inflammatory marker Lipocalin-2 as well as delayed lethality after gastrointestinal MNV infection. Together, these results uncover new insights into the mechanisms of norovirus-induced inflammation and cell death, thereby revealing Nlrp3 inflammasome activation and ensuing GSDMD-driven pyroptosis as contributors to MNV-induced immunopathology in susceptible STAT1-deficient mice.
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