Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf

Miao, Edward A; Alpuche-Aranda, Celia M; Dors, Monica; Clark, April E; Bader, Martin W; Miller, Samuel I; Aderem, Alan

doi:10.1038/ni1344

Cited by 1,127Inflammasome and immune disordersImmune Response and InflammationSalmonella and Campylobacter epidemiology

Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf

Miao, Edward A, Alpuche-Aranda, Celia M, Dors, Monica, Clark, April E, Bader, Martin W, Miller, Samuel I, Aderem, Alan·2006·Nature Immunology

DOI 10.1038/ni1344

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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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IL-1β production was independent of the Ipaf inflammasome.
“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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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
ORCID: Miao, Edward A
Alpuche-Aranda, Celia M
Miller, Samuel I
Aderem, Alan
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2006-04-30
Volume: 7
Issue: 6
Pages: 569-575
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni1344
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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Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf

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