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

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Miao, Edward A.
    • Other Affiliation: Institute for Systems Biology
  • Alpuche-Aranda, Celia M.
    • Other Affiliation: Experimental Medicine, Medical School, Universidad Nacional Autonoma de Mexico-Hospital Infantil de Mexico Federico Gomez
  • Dors, Monica
    • Other Affiliation: Institute for Systems Biology
  • Clark, April E.
    • Other Affiliation: Institute for Systems Biology
  • Bader, Martin W.
    • Other Affiliation: Department of Microbiology, University of Washington
  • Miller, Samuel I.
    • Other Affiliation: Department of Microbiology, University of Washington
  • Aderem, Alan
    • Other Affiliation: Institute for Systems Biology
Abstract
  • Macrophages respond to Salmonella typhimurium infection via Ipaf, a NACHT–leucine-rich repeat family member that activates caspase-1 and secretion of interleukin 1β. 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.
Date of publication
DOI
Identifier
Related resource URL
Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Nature Immunology
Journal volume
  • 7
Journal issue
  • 6
Page start
  • 569
Page end
  • 575
Language
  • English
Version
  • Postprint
ISSN
  • 1529-2916

Relations

Parents:

This work has no parents.

Items

Thumbnail Title Date Uploaded Visibility Actions
file details Cytoplasmic flagellin activates caspase-1.pdf 2019-05-03 Public Download