ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Neutrophil IL-1β processing induced by pneumolysin is mediated by the NLRP3/ASC inflammasome and caspase-1 activation and is dependent on K+ efflux.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.
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Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 227 citations in OpenAlex.
- Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review.PloS one · 2023Pooled it
- Streptococcus anginosus activates the NLRP3 inflammasome to promote inflammatory responses from macrophages.Journal of leukocyte biology · 2026Article
- Sensing the spectrum: diverse stimuli for the NLRP3 inflammasome.Communications biology · 2026Review
- NLRP3 inflammasome promotes PAD2/PAD4 release and protein citrullination in rheumatoid arthritis.Communications biology · 2026Article
- α-hemolysin polymorphisms in methicillin-resistantbioRxiv : the preprint server for biology · 2025Article
- IL-1 family cytokines in inflammation and immunity.Cellular & molecular immunology · 2025Review
- NLRP3 inflammasome in acute lung injury: Cumulative evidence for traditional Chinese medicine and natural products.Chinese herbal medicines · 2025Review
- New Insights on the Potential Role of Pyroptosis in Parkinson's Neuropathology and Therapeutic Targeting of NLRP3 Inflammasome with Recent Advances in Nanoparticle-Based miRNA Therapeutics.Molecular neurobiology · 2025Review
- Review
- Article
- NLRP3 Inflammasome Activation Modulates Neutrophil Extracellular Trap Formation and Aggravates Airway Inflammation in Bronchiectasis.Research (Washington, D.C.) · 2025Article
- Macrophage pyroptosis mediates hyperoxia-induced inflammatory lung injury in neonates.Frontiers in immunology · 2025Article
- Neutrophil pyroptosis regulates corneal wound healing and post-injury neovascularisation.Clinical and translational medicine · 2024Article
- Gasdermins as evolutionarily conserved executors of inflammation and cell death.Nature cell biology · 2024Review
- Article
- Neutrophil Heterogeneity Is Modified during Acute Lung Inflammation in Apoa1-/- Mice.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Lack of Annexin A1 Exacerbates Inflammatory Response in Acute Endometritis Model.Inflammation · 2024Article
- The gasdermin family: emerging therapeutic targets in diseases.Signal transduction and targeted therapy · 2024Review
- Inherently Reduced Expression of ASC Restricts Caspase-1 Processing in Hepatocytes and Promotes Plasmodium Infection.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- NLRP3 Activation Contributes to Memory Impairment in an Experimental Model of Pneumococcal Meningitis.Molecular neurobiology · 2024Article
89 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
Although neutrophils are the most abundant cells in acute infection and inflammation, relatively little attention has been paid to their role in inflammasome formation and IL-1β processing. In the present study, we investigated the mechanism by which neutrophils process IL-1β in response to Streptococcus pneumoniae. Using a murine model of S. pneumoniae corneal infection, we demonstrated a requirement for IL-1β in bacterial clearance, and we showed that Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and caspase-1 are essential for IL-1β production and bacterial killing in the cornea. Neutrophils in infected corneas had multiple specks with enzymatically active caspase-1 (YVAD-FLICA 660), and bone marrow neutrophils stimulated with heat-killed S. pneumoniae (signal 1) and pneumolysin (signal 2) exhibited multiple specks when stained for NLRP3, ASC, or Caspase-1. High-molecular mass ASC complexes were also detected, consistent with oligomer formation. Pneumolysin induced K(+) efflux in neutrophils, and blocking K(+) efflux inhibited caspase-1 activation and IL-1β processing; however, neutrophils did not undergo pyroptosis, indicating that K(+) efflux and IL-1β processing is not a consequence of cell death. There was also no role for lysosomal destabilization or neutrophil elastase in pneumolysin-mediated IL-1β processing in neutrophils. Taken together, these findings demonstrate an essential role for neutrophil-derived IL-1β in S. pneumoniae infection, and they elucidate the role of the NLRP3 inflammasome in cleavage and secretion of IL-1β in neutrophils. Given the ubiquitous presence of neutrophils in acute bacterial and fungal infections, these findings will have implications for other microbial diseases.
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