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

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

Research output: Contribution to journalArticle

393 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

Fingerprint

Inflammasomes
Caspase 1
Toll-Like Receptors
Adenosine Triphosphate
Purinergic P2X7 Receptors
Flagellin
Interleukin-1
Lipopolysaccharides
Ligands
Bacteria

Keywords

  • CELLIMMUNO
  • MOLIMMUNO
  • SIGNALING

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Pannexin-1-Mediated Recognition of Bacterial Molecules Activates the Cryopyrin Inflammasome Independent of Toll-like Receptor Signaling. / Kanneganti, Thirumala Devi; Lamkanfi, Mohamed; Kim, Yungi; Chen, Grace; Park, Jong Hwan; Franchi, Luigi; Vandenabeele, Peter; Núñez, Gabriel.

In: Immunity, Vol. 26, No. 4, 27.04.2007, p. 433-443.

Research output: Contribution to journalArticle

Kanneganti, TD, Lamkanfi, M, Kim, Y, Chen, G, Park, JH, Franchi, L, Vandenabeele, P & Núñez, G 2007, 'Pannexin-1-Mediated Recognition of Bacterial Molecules Activates the Cryopyrin Inflammasome Independent of Toll-like Receptor Signaling', Immunity, vol. 26, no. 4, pp. 433-443. https://doi.org/10.1016/j.immuni.2007.03.008
Kanneganti, Thirumala Devi ; Lamkanfi, Mohamed ; Kim, Yungi ; Chen, Grace ; Park, Jong Hwan ; Franchi, Luigi ; Vandenabeele, Peter ; Núñez, Gabriel. / Pannexin-1-Mediated Recognition of Bacterial Molecules Activates the Cryopyrin Inflammasome Independent of Toll-like Receptor Signaling. In: Immunity. 2007 ; Vol. 26, No. 4. pp. 433-443.
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