Activation of the NLRP3 inflammasome by intracellular poly I:C.
Several RNA viruses can be detected by the inflammasome, which promotes IL-1β and IL-18 secretion, but the underlying mechanisms of detection remain unclear. Cytosolic dsRNA is a replication intermediate of many RNA viruses. We show here that transfection of the dsRNA analogue poly I:C activates the NLRP3 inflammasome via a pathway requiring endosomal acidification. This detection is independent of the other poly I:C sensors: TLR3 and MDA5. These results suggest a mechanism by which cytosolic dsRNA produced during viral infection could activate the NLRP3 inflammasome.
Institute for Systems Biology, Seattle, WA 98103, USA.
Jayant V
JV
Rajan
Sarah E
SE
Warren
Edward A
EA
Miao
Alan
A
Aderem
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004279:DNA, Viral / Q000737:chemistry; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D018274:Electroporation; D011992:Endosomes / Q000737:chemistry; D005260:Female; D006863:Hydrogen-Ion Concentration; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism*; D008024:Ligands; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011070:Poly I-C / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection
D002352:Carrier Proteins; D004279:DNA, Viral; D058847:Inflammasomes; D053583:Interleukin-1beta; D008024:Ligands; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D011070:Poly I-C