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PMID:17008311
| Citation |
Kanneganti, TD, Body-Malapel, M, Amer, A, Park, JH, Whitfield, J, Franchi, L, Taraporewala, ZF, Miller, D, Patton, JT, Inohara, N and Núñez, G (2006) Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J. Biol. Chem. 281:36560-8 |
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| Abstract |
Viral infection induces the production of interleukin (IL)-1beta and IL-18 in macrophages through the activation of caspase-1, but the mechanism by which host cells sense viruses to induce caspase-1 activation is unknown. In this report, we have identified a signaling pathway leading to caspase-1 activation that is induced by double-stranded RNA (dsRNA) and viral infection that is mediated by Cryopyrin/Nalp3. Stimulation of macrophages with dsRNA, viral RNA, or its analog poly(I:C) induced the secretion of IL-1beta and IL-18 in a cryopyrin-dependent manner. Consistently, caspase-1 activation triggered by poly(I:C), dsRNA, and viral RNA was abrogated in macrophages lacking cryopyrin or the adaptor ASC (apoptosis-associated speck-like protein containing a caspase-activating and recruitment domain) but proceeded normally in macrophages deficient in Toll-like receptor 3 or 7. We have also shown that infection with Sendai and influenza viruses activates the cryopyrin inflammasome. Finally, cryopyrin was required for IL-1beta production in response to poly(I:C) in vivo. These results identify a mechanism mediated by cryopyrin and ASC that links dsRNA and viral infection to caspase-1 activation resulting in IL-1beta and IL-18 production. |
| Links |
PubMed Online version:10.1074/jbc.M607594200 |
| Keywords |
Animals; Bone Marrow Cells/cytology; Carrier Proteins/metabolism; Carrier Proteins/physiology; Caspase 1/metabolism; Cytoskeletal Proteins/physiology; Enzyme Activation; Interleukin-18/metabolism; Interleukin-1beta/metabolism; Ligands; Macrophages/metabolism; Mice; Mice, Knockout; Orthomyxoviridae/metabolism; RNA, Double-Stranded/chemistry; Sendai virus/metabolism |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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