ReviewInflammasomePriminginSterileInflammatoryDiseaseMeghanaN.Patel,1RichardG.Carroll,1,2SilviaGalván-Peña,1,2EvannaL.Mills,1,2RobinOlden,1,3MarthaTriantafilou,1,3AmayaI.Wolf,4ClareE.Bryant,1,5KathyTriantafilou,1,3andSethL.Masters1,6,7,*Theinflammasomeisacytoplasmicproteincomplexthatprocessesinterleu-kins(IL)-1bandIL-18,anddrivesaformofcelldeathknownaspyroptosis.Oligomerizationofthiscomplexisactuallythesecondstepofactivation,andaprimingstepmustoccurfirst.Thisinvolvestranscriptionalupregulationofpro-IL-1b,inflammasomesensorNLRP3,orthenon-canonicalinflammasomesensorcaspase-11.Anadditionalaspectofprimingisthepost-translationalmodificationofparticularinflammasomeconstituents.PrimingistypicallyaccomplishedinvitrousingamicrobialToll-likereceptor(TLR)ligand.How-ever,itisnowclearthatinflammasomesareactivatedduringtheprogressionofsterileinflammatorydiseasessuchasatherosclerosis,metabolicdisease,andneuroinflammatorydisorders.Therefore,itistimetoconsidertheendogenousfactorsandmechanismsthatmayprimetheinflammasomeintheseconditions.InnateImmunityandtheInflammasomeTheinnateimmunesystemisspecializedtoperformreceptor-mediatedsurveillanceforpathogenand/ortissuedamage.Patternrecognitionreceptors(PRRs,see[27_TD$DIF]Glossary)arethefirstlineofdefenseagainstinvadingmicrobesandareexpressedinavarietyofimmunecellsincludingmacrophages,epithelialcells,dendriticcells,neutrophils,andadaptiveimmunecells.SomeofthesePRRs,suchastheTLRsandC-typelectins(CTLs),areexpressedonthecellsurfaceandcanbeactivateddirectlyviaexternalpathologicalsignalsknownaspathogen-associatedmolecularpatterns(PAMPs).PRRsarealsotriggeredduringsterileinflam-matorydiseases,suggestingacrucialrolefordangersignalsthatarenotforeignbutareinsteadhost-derived.Theseareknownasdanger-associatedmolecularpatterns(DAMPs).BothPAMPsandDAMPscanalsomaketheirwayintothecellwheretheycantriggerintracellularinnateimmunereceptorsdirectly,forexampleviarecognitionofDNAorRNAinthecytoplasm.Somecytosolicinnateimmunesensorsarealsoactivatedindirectlyasa...
