Pannexin-1-Mediated Recognition of Bacterial Molecules Activates the Cryopyrin Inflammasome Independent of Toll-like Receptor Signaling

Thirumala Devi Kanneganti, Mohamed Lamkanfi, Yun Gi Kim, Grace Chen, Jong Hwan Park, Luigi Franchi, Peter Vandenabeele, Gabriel Núñez

Research output: Contribution to journalArticle

406 Citations (Scopus)

Abstract

Cryopyrin is essential for caspase-1 activation triggered by Toll-like receptor (TLR) ligands in the presence of adenosine triphosphate (ATP). However, the events linking bacterial products and ATP to cryopyrin remain unclear. Here we demonstrate that cryopyrin-mediated caspase-1 activation proceeds independently of TLR signaling, thus dissociating caspase-1 activation and IL-1β secretion. Instead, caspase-1 activation required pannexin-1, a hemichannel protein that interacts with the P2X7 receptor. Direct cytosolic delivery of multiple bacterial products including lipopolysaccharide, but not flagellin, induced caspase-1 activation via cryopyrin in the absence of pannexin-1 activity or ATP stimulation. However, unlike Ipaf-dependent caspase-1 activation, stimulation of the pannexin-1-cryopyrin pathway by several intracellular bacteria was independent of a functional bacterial type III secretion system. These results provide evidence for cytosolic delivery and sensing of bacterial molecules as a unifying model for caspase-1 activation and position pannexin-1 as a mechanistic link between bacterial stimuli and the cryopyrin inflammasome.

Original languageEnglish
Pages (from-to)433-443
Number of pages11
JournalImmunity
Volume26
Issue number4
DOIs
Publication statusPublished - 2007 Apr 27
Externally publishedYes

Keywords

  • CELLIMMUNO
  • MOLIMMUNO
  • SIGNALING

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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