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 language | English |
|---|---|
| Pages (from-to) | 433-443 |
| Number of pages | 11 |
| Journal | Immunity |
| Volume | 26 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2007 Apr 27 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Pannexin-1-Mediated Recognition of Bacterial Molecules Activates the Cryopyrin Inflammasome Independent of Toll-like Receptor Signaling
AU - Kanneganti, Thirumala Devi
AU - Lamkanfi, Mohamed
AU - Kim, Yungi
AU - Chen, Grace
AU - Park, Jong Hwan
AU - Franchi, Luigi
AU - Vandenabeele, Peter
AU - Núñez, Gabriel
PY - 2007/4/27
Y1 - 2007/4/27
N2 - 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.
AB - 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.
KW - CELLIMMUNO
KW - MOLIMMUNO
KW - SIGNALING
UR - http://www.scopus.com/inward/record.url?scp=34247118826&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34247118826&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2007.03.008
DO - 10.1016/j.immuni.2007.03.008
M3 - Article
C2 - 17433728
AN - SCOPUS:34247118826
VL - 26
SP - 433
EP - 443
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 4
ER -