CCL2 expression is mediated by type I IFN receptor and recruits NK and T cells to the lung during MVA infection

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

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...

【 授权许可】

CC BY