Crosstalk between autophagy and inflammatory signaling pathways-balancing host defence and homeostasis.pdfVIP免费

Crosstalkbetweenautophagyandinflammatorysignalingpathways:balancinghostdefenceandhomeostasisKenCadwell1,21KimmelCenterforBiologyandMedicineattheSkirballInstitute,NewYorkUniversitySchoolofMedicine,NewYork,NY10016,USA2DepartmentsofMicrobiologyandMedicine,NewYorkUniversitySchoolofMedicine,NewYork,NY10016,USAAbstractAutophagyhasbroadfunctionsinimmunityrangingfromcellautonomousdefensetocoordinationofcomplexmulticellularresponses.Thesuccessfulresolutionofinfectionandavoidanceofautoimmunitynecessitatesefficientandtimelycommunicationbetweenautophagyandpathwaysthatsensetheimmuneenvironment.Inthisarticle,progressinelucidatingmechanismsofcrosstalkbetweenautophagyandinflammatorysignalingcascadeswillbereviewed.Therecentliteratureindicatesthatavarietyofimmunemediatorsinduceorrepressautophagy.Itisalsobecomingincreasingclearthatimmunesignalingcascadesaresubjecttoregulationbyautophagy,andthatareturntohomeostasisfollowingarobustimmuneresponseiscriticallydependentonthispathway.Importantly,examplesofnon-canonicalformsofautophagyinmediatingimmunityarepervasive.Improvedmechanisticunderstandingoftheautophagymachineryoffershopefortreatinginfectiousandinflammatorydiseases.Macroautophagy,morecommonlyreferredtosimplyasautophagy,isafundamentalcellularprocessineukaryotesthatisessentialforrespondingandadaptingtochangesintheenvironment.Initsmostcommonform,autophagyinvolvessequestrationofcytosolicmaterialwithinadoublemembrane-boundvesicletermedtheautophagosome,andthesubsequentfusionoftheautophagosomewithendolysosomalvesiclesleadstodegradationandrecyclingofsequesteredsubstrates.Acriticalfunctionofautophagyistobreakdownmacromoleculessuchasproteinstoprovideaminoacidsandotherfactorsnecessarytogenerateenergyandsynthesizenewproteins.Theabilitytocapturelargematerialdistinguishesthispathwayfromproteasomaldegradation,makingautophagycriticalformaintainingcellularhomeostasisinavarietyofsettings.Manyofthesubstratesfoundwithinautophagosomesarethosethatthreatencellviability,suchasdamagedorganelles,proteinagg...