ImmunologicalReviews.2017;277:61–75.wileyonlinelibrary.com/journal/imr|61©2017JohnWiley&SonsA/S.PublishedbyJohnWiley&SonsLtdDOI:10.1111/imr.12534INVITEDREVIEWMolecularmechanismsandfunctionsofpyroptosis,inflammatorycaspasesandinflammasomesininfectiousdiseasesSiMingMan|RajendraKarki|Thirumala-DeviKannegantiDepartmentofImmunology,St.JudeChildren’sResearchHospital,Memphis,TN,USACorrespondenceThirumala-DeviKanneganti,DepartmentofImmunology,St.JudeChildren’sResearchHospital,Memphis,TN,USA.Email:thirumala-devi.kanneganti@stjude.orgFundinginformationWorkfromourlaboratoryissupportedbytheUSNationalInstitutesofHealth(AI101935,AI124346,AR056296,andCA163507toT.D.K.)andALSAC(toT.D.K.)SummaryCelldeathisafundamentalbiologicalphenomenonthatisessentialforthesurvivalanddevelopmentofanorganism.Emergingevidencealsoindicatesthatcelldeathcontributestoimmunedefenseagainstinfectiousdiseases.Pyroptosisisaformofin-flammatoryprogrammedcelldeathpathwayactivatedbyhumanandmousecaspase-1,humancaspase-4andcaspase-5,ormousecaspase-11.Theseinflammatorycaspasesareusedbythehosttocontrolbacterial,viral,fungal,orprotozoanpatho-gens.Pyroptosisrequirescleavageandactivationofthepore-formingeffectorproteingasderminDbyinflammatorycaspases.Physicalruptureofthecellcausesreleaseofthepro-inflammatorycytokinesIL-1βandIL-18,alarminsandendogenousdanger-associatedmolecularpatterns,signifyingtheinflammatorypotentialofpyroptosis.Here,wedescribethecentralroleofinflammatorycaspasesandpyroptosisinmediat-ingimmunitytoinfectionandclearanceofpathogens.KEYWORDSbacteria,caspase-1,caspase-11,caspase-4,caspase-5,celldeath,gasderminD,infection,inflammasomes,inflammation,inflammatorycaspases,interferons,lysis,lytic,necroptosis,necrosis,pores,pyroptosis,viruses1|INTRODUCTIONProgrammedcelldeathpathways,includingapoptosis,pyroptosis,andnecroptosis,areregulatedbyuniquesetsofhostproteinsthatcoor-dinateavarietyofbiologicaloutcomes.1–6Bothapoptosisandpyrop-tosisareexecutedbycaspases.Apoptosisismediatedbyapoptoticcaspases,whichin...
