Immunity
Volume 26, Issue 4, 27 April 2007, Pages 433-443
Journal home page for Immunity

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

https://doi.org/10.1016/j.immuni.2007.03.008Get rights and content
Under an Elsevier user license
open archive

Summary

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.

SIGNALING
CELLIMMUNO
MOLIMMUNO

Cited by (0)

4

These authors contributed equally to this work.