Recombinant human mannose‐binding lectin dampens human alveolar macrophage inflammatory responses to influenza A virus in vitro

[摘要] IAVpneumoniaremainsaseriousglobalhealthproblem,andpreventativeandtherapeuticstrategiesremainlimited.AMarecriticaleffectorcellsinthecontrolofinfluenza,impairingIAVreplication,promotingIAVclearance,andpromotingefferocytosisandresolutionoflunginflammation.MBL,aninnateimmunepatternrecognitionmolecule,presentinthelungs,bindsIAV,andplasmaMBLdeficiencyisassociatedwithincreasedsusceptibilitytoIAV,althoughthemechanismremainsincompletelyunderstood,andtheinfluenceofMBLontheIAV‐AMinteractionhasnotbeenestablished.Inthecurrentstudy,focusingonhumanmacrophages(U937celllineandclinicallyrelevanthumanAM),datademonstratedthatunopsonizedIAVisreadilyinternalized,inducedreleaseofTNFandROS,andpromotedmacrophageapoptosis.Incontrast,IAV,opsonizedwithrhMBL,reducedIAVuptakeandmacrophageapoptosisanddramaticallyreducedTNFreleaseandROS.Macrophagehost‐defenseresponseswerereducedfurtherinthepresenceofMASPs.Takentogether,thesedatasupporttheconceptthatrhMBLmayserveaprotectiveinnatehostresponseandacriticalbiologicalresponsemodifierfunctionbylimitingAMinflammation,oxidativeinjury,andAMapoptosis,whichmayalloweffectiveIAVclearancewhilelimitingcollateraldamagetovitalorgans,suchasthelungs...

[学科分类] 生理学

[关键词] innate immunity;C‐type lecin;TNF;respiratory burst;apoptosis;biological response modifier