Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
CCL2 expression is mediated by type I IFN receptor and recruits NK and T cells to the lung during MVA infection | |
关键词: cell migration; chemokine; interferon; lung; vaccinia virus; | |
DOI : 10.1189/jlb.4MA0815-376RR | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
Migrationofleukocytestothesiteofmicrobialinfectionisimportantforthedevelopmentofeffectivehostimmunity.RecombinantmodifiedvacciniavirusAnkaraisfrequentlyusedasaviralvectorvaccineinpreclinicalandclinicalstudies.Incomparisontoothervacciniavirusstrains,modifiedvacciniavirusAnkararobustlyinduceschemokineexpressionandrapidattractionofleukocytes.Inparticular,chemokine(C‐Cmotif)ligand2(CCL2)hasbeenshowntobecriticalforleukocyterecruitmenttothelung.Inthisstudy,MVA‐inducedCCL2expressioninmurinemacrophageswasdependentontypeIinterferonreceptorandnotToll‐likereceptor‐2.ThecriticalroleoftypeIinterferonreceptorsignalingforCCL2productioninthelungwasconfirmedintypeIinterferonreceptor–deficientmice(Ifnar1−/−).Inaddition,comparingIfnar1−/−andCcl2−/−micewithwild‐typemice,weobservedasimilarimpairmentintherecruitmentofnaturalkillerandTcellstothelungafterintranasalinfectionwithmodifiedvacciniavirusAnkara.Conversely,neutrophilrecruitmentwasnotaffectedinIfnar1−/−andCcl2−/−mice.WeconcludethattypeIinterferons,besidestheirknownantiviralproperties,caninitiatetherecruitmentandactivationofleukocytesviainductionofchemokineexpressionincludingCCL2...
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