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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Miao, EA; Alpuche-Aranda, CM; Dors, M; Clark, AE; Bader, MW; Miller, SI; Aderem, A

Published Date

  • June 2006

Published In

Volume / Issue

  • 7 / 6

Start / End Page

  • 569 - 575

PubMed ID

  • 16648853

Pubmed Central ID

  • 16648853

Electronic International Standard Serial Number (EISSN)

  • 1529-2916

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni1344

Language

  • eng