Pannexin-1-Mediated Recognition of Bacterial Molecules Activates the Cryopyrin Inflammasome Independent of Toll-like Receptor Signaling
Top Cited Papers
Open Access
- 1 April 2007
- journal article
- research article
- Published by Elsevier BV in Immunity
- Vol. 26 (4), 433-443
- https://doi.org/10.1016/j.immuni.2007.03.008
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.Keywords
Funding Information
- National Institutes of Health (A/064748, AI063331, GOA 12.0505.02, IAP6/18, SCIE2003-48)
This publication has 47 references indexed in Scilit:
- Pannexin1 is part of the pore forming unit of the P2X7 receptor death complexFEBS Letters, 2007
- Pannexin-1 mediates large pore formation and interleukin-1β release by the ATP-gated P2X7 receptorThe EMBO Journal, 2006
- Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infectionThe Journal of Experimental Medicine, 2006
- TLR signalingCell Death & Differentiation, 2006
- Cryopyrin activates the inflammasome in response to toxins and ATPNature, 2006
- Arabidopsis RIN4 Is a Target of the Type III Virulence Effector AvrRpt2 and Modulates RPS2-Mediated ResistanceCell, 2003
- Nod1, a CARD protein, enhances pro-interleukin-1β processing through the interaction with pro-caspase-1Biochemical and Biophysical Research Communications, 2002
- RIN4 Interacts with Pseudomonas syringae Type III Effector Molecules and Is Required for RPM1-Mediated Resistance in ArabidopsisCell, 2002
- Delivery of proteins into living cells by reversible membrane permeabilization with streptolysin-OProceedings of the National Academy of Sciences of the United States of America, 2001
- A novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytesNature, 1992