LeadingEdgeReviewTheInflammasomesKateSchroder1,2andJurgTschopp1,*1DepartmentofBiochemistry,UniversityofLausanne,CH-1066Epalinges,Switzerland2MonashInstituteofMedicalResearch,MonashUniversity,Melbourne,Victoria3800,Australia*Correspondence:jurg.tschopp@unil.chDOI10.1016/j.cell.2010.01.040Inflammasomesaremolecularplatformsactivateduponcellularinfectionorstressthattriggerthematurationofproinflammatorycytokinessuchasinterleukin-1btoengageinnateimmunedefenses.Strongassociationsbetweendysregulatedinflammasomeactivityandhumanheritableandacquiredinflammatorydiseaseshighlighttheimportancethispathwayintailoringimmuneresponses.Here,wecomprehensivelyreviewmechanismsdirectingnormalinflammasomefunc-tionanditsdysregulationindisease.AgonistsandactivationmechanismsoftheNLRP1,NLRP3,IPAF,andAIM2inflammasomesarediscussed.Regulatorymechanismsthatpotentiateorlimitinflammasomeactivationareexamined,aswellasemerginglinksbetweentheinflammasomeandpyroptosisandautophagy.Traditionally,innateimmunityhasbeenviewedasthefirstlineofdefensediscriminating‘‘self’’(e.g.,hostproteins)from‘‘nonself’’(e.g.,microorganisms).However,emergingliteraturesuggeststhatinnateimmunityactuallyservesasasophisticatedsystemforsensingsignalsof‘‘danger,’’suchaspathogenicmicrobesorhost-derivedsignalsofcellularstress,whileremainingunre-sponsivetonondangerousmotifs,suchasnormalhostmole-cules,dietaryantigens,orcommensalgutflora.ThenotionthatinnateimmunityfunctionsasadangersentinelhassimilaritiestoMatzinger’s‘‘dangerhypothesis,’’proposedforadaptiveimmuneresponses(Matzinger,1994).Suchamodelforrecog-nizingsituationsofhostdangerallowsforcoordinateactivationofimmunesystemantimicrobialandtissuerepairfunctionsinresponsetoinfectionorinjury,whileavoidingcollateraldamageinsituationsinwhichharmlessnonselfispresent.Theinnateimmunesystemengagesanarrayofgermline-encodedpattern-recognitionreceptors(PRRs)todetectinvari-antmicrobialmotifs.PRRsareexpressedbycellsatthefrontlineofdefenseagainstinfection,includingmacrophages,mo...
