Articleshttps://doi.org/10.1038/s41590-017-0042-61DepartmentofCancerImmunology,Genentech,SouthSanFrancisco,CA,USA.2DepartmentofMicrochemistry,Proteomics&Lipidomics,Genentech,SouthSanFrancisco,CA,USA.3DepartmentofTranslationalImmunology,Genentech,SouthSanFrancisco,CA,USA.4DepartmentofBioinformatics&ComputationalBiology,Genentech,SouthSanFrancisco,CA,USA.5BiomarkerDiscoveryOMNI,Genentech,SouthSanFrancisco,CA,USA.6DepartmentofImmunology,Genentech,SouthSanFrancisco,CA,USA.*e-mail:murthy.aditya@gene.comAdvancesinhumangeneticsandthestudyofhost–microbeinteractionshavesignificantlyimprovedtheunderstand-ingofhowhost–environmentcommunicationmodulatesdiseaserisk1,2.Sittingatthisintersection,autophagyhasemergedasakeyprotectivepathwaythatactsthroughtheclearanceofintracellularpathogensandinductionofimmunosuppression3,4.Macroautophagy(called‘autophagy’here)involvestheengulf-mentofcytosoliccargointoadouble-membranedstructurewhosesubsequentfusionwithlysosomestriggersdegradationofthevesicularcontents5,6.Sequestosome-likereceptors(SLRs)promotetheassociationofcargowithmembraneproteinsoftheLC3orGABARAPLsubfamily7.Functionallydistinctformsofautophagyhavebeenidentifiedthatguidetheclearanceofintracellularpatho-gens(xenophagy),damagedand/oragedorganelles(forexample,mitophagy,endoplasmicreticulum(ER)-phagy,nucleophagyandpexophagy)andproteinaggregates(aggrephagy)8.Defectiveautophagyconfersapro-inflammatoryphenotypeinresponsetovariouscellularstresses,whereasgermlinevariantsoftheautoph-agy-relatedgenesAtg16l1andAtg5lareassociatedwithchronicinflammatorydisease1,9.Moreover,componentsoftheautophagymachineryareupregulatedaftermicrobe-associatedmolecularpat-ternsaresensedbymacrophages,dendriticcellsandneutrophils10,11.Pattern-recognitionreceptorssuchasTLRsengagemicrobe-asso-ciatedmolecularpatternsatextracellularcompartments,includingtheplasmamembrane,aswellasinendosomalorendolysosomallumens12.EngagementofaTLRinitiatesinflammatorysignalingviaoneoftwomajoradaptors:TIRAP–MYD88orTRAM–TRIF13.TLR...
