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Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf
Abstract
Macrophages respond to Salmonella typhimurium infection via Ipaf, a NACHT-leucine-rich repeat family member that activates caspase-1 and secretion of interleukin 1beta. However, the specific microbial salmonella-derived agonist responsible for activating Ipaf is unknown. We show here that cytosolic bacterial flagellin activated caspase-1 through Ipaf but was independent of Toll-like receptor 5, a known flagellin sensor. Stimulation of the Ipaf pathway in macrophages after infection required a functional salmonella pathogenicity island 1 type III secretion system but not the flagellar type III secretion system; furthermore, Ipaf activation could be recapitulated by the introduction of purified flagellin directly into the cytoplasm. These observations raise the possibility that the salmonella pathogenicity island 1 type III secretion system cannot completely exclude 'promiscuous' secretion of flagellin and that the host capitalizes on this 'error' by activating a potent host-defense pathway.
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“By contrast, IL-1β production was independent of the Ipaf inflammasome, which has been shown to activate caspase-1 and produce IL-1β in response to flagellin from Salmonella typhimurium and Legionella pneumophila (fig.S4) (11,12).”
From Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica (2008) · cites this paper as [11]
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Metadata
- Authors
- Miao, E. A., Alpuche-Aranda, C. M., Dors, M., Clark, A. E., Bader, M. W., Miller, S. I., & Aderem, A.
- Affiliations
- University of Washington (US)
- Hospital Infantil de México Federico Gómez (MX)
- Institute for Systems Biology (US)
- Corresponding author
- Aderem, Alan
- Venue
- Nature Immunology
- Published
- 2006-04-30
- Volume
- 7
- Issue
- 6
- Pages
- 569-575
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W1987463569
- Cited by
- 1,127
- References
- 45
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 32 · 2023: 49 · 2022: 48 · 2021: 37 · 2020: 50 · 2019: 51 · 2018: 44 · 2017: 56 · 2016: 47 · 2015: 56 · 2014: 78 · 2013: 85 · 2012: 70
- FWCI
- 33.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Genentech
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
- Keywords
- caspase-1 activation, interleukin-1β secretion, interstitial pneumonia with autoimmune features, Salmonella typhimurium, macrophages, pathogenicity island 1, type III secretion system, TLR5, innate immunity
- MeSH terms
- Animals, Bacterial Proteins, Calcium-Binding Proteins, Cytoplasm, Enzyme Activation, Flagellin, Interleukin-1, Macrophages, Mice, Mutant Strains, Mutation, Salmonella Infections, Salmonella typhimurium, Caspase 1, Protein Transport, Apoptosis Regulatory Proteins, Toll-Like Receptor 5, Mice
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