Respiratory syncytial virus infection modifies and accelerates pulmonary disease via DC activation and migration

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: immune responses;    cytokines;    T cells;   

DOI  :  10.1189/jlb.0412195

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inthepresentstudies,wehaveestablishedthatRSVcanelicitamorepathogenicenvironmentdependentonimproperDC‐associatedsensitization.OurinitialstudiesdemonstratedthatRSV,butnotinfluenza,infectionduringanallergenexposureintotheairwayinducedamoresevereallergenresponse.TheRSV‐inducedexacerbationincludedanincreasedTh2cytokineresponseandpathophysiologyasmonitoredbyAHRandmucusoverproduction.DCsplayedacentralroleintheallergen‐inducedresponses,asinstillingRSV‐infectedBMDCintotheairwaycouldrecapitulatealiveviruschallenge.WiththeuseofCCR6−/−micethathaveaprimarydefectintherecruitmentofmDCsubsets,reducedexacerbationofdiseasewasobservedwhenRSVwasadministeredalongwithallergen.Furthermore,sensitizationofmicewithRSV‐infectedBMDCintotheairwayproducedamoresevereimmuneresponsetoaliveviruschallenge.Subsequently,usingRSV‐infectedBMDCfromCCR7−/−mice(thatdonotmigrateefficientlytoLNs)tosensitizetheexacerbatedresponsedemonstratedthattheresponsewasdependentonDCmigrationtotheLN.Finally,theabilityofRSV‐infectedDCstoelicitanexacerbated,allergen‐inducedpathogenicresponsecouldbemaintainedforaslongas3weeks,suggestingthatRSV‐infectedDCsthemselvescreatedanalteredimmuneenvironmentthatimpactsoff‐targetmucosalresponsesthatcouldhaveprolongedeffects...

【 授权许可】

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