TLR9 and TLR7 agonists mediate distinct type I IFN responses in humans and nonhuman primates in vitro and in vivo

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

关键词: interferon subtypes;    CpG ODN;    imiquimod;    macaques;    skin;   

DOI  :  10.1189/jlb.0711371

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

HumanI‐IFNsincludeIFN‐βand13independentlyregulatedsubtypesofIFN‐α(I‐IFNs).TLR7and‐9induceI‐IFNs,butitisunknownwhethertheirsubtyperepertoireissimilar.ThisstudyusednewPCRarraysthatselectivelyamplifyindividualI‐IFNsubtypegenesofhumanandnonhumanprimatestocharacterizetheTLR7‐and‐9‐mediatedIFNresponseinvitroandinvivo.WeshowthatinhumanPBMCs,TLR7agonistsinducearapidburstofI‐IFNtranscripts,consistingprimarilyofIFN‐α1/13,‐α2,and‐α14.Incontrast,TLR9agonists,regardlessofthetypeused(CpGC‐,B‐,orD‐ODN),promptedslowerbutsustainedexpressionofIFN‐α1/13,‐α2,‐α7,‐α8,‐α10,‐α14,‐α16,and‐α21.ThesequalitativedifferencesweretranslateddownstreamasdifferencesinthepatternofIFN‐induciblegenes.InmacaquePBMCs,imiquimodproducedashortburstofIFNmRNA,dominatedbyIFN‐α8,whereasC‐orD‐ODNinducedagreaterthantenfoldincreaseintranscriptsforallI‐IFNsubtypesby12hofculture.Differencesweremoreevidentinvivo,whereTLR7and‐9agonistsinducedsignificantlydifferentlevelsofI‐IFNtranscriptsinskin.AlthoughtheratesofgenetranscriptiondifferedsignificantlyforindividualTLR9agonists,theirIFN‐αsubtypesignaturewasalmostidentical,indicatingthatthetypeofreceptordictatesthequalityoftheI‐IFNresponseinvitroandinvivo.TheseresultsmayunderliethedifferentialtherapeuticeffectsofTLR7and‐9agonistsandshouldinformfutureclinicalstudies...

【 授权许可】

CC BY