Cutting edge: innate immune system discriminates between RNA containing bacterial versus eukaryotic structural features that prime for high-level IL-12 secretion by dendritic cells.
RNA derived from bacterial but not eukaryotic sources, when transfected into human monocyte-derived dendritic cell precursors, induces high-level IL-12 secretion in conjunction with dendritic cell maturation stimuli. In vitro-transcribed mRNA that mimics the structure of bacterial mRNA in the lack of a long 3'-poly(A) tail likewise induces IL-12 secretion, but this property is lost upon efficient enzymatic 3'-polyadenylation. Among other tested RNAs, only polyuridylic acid induced IL-12 p70. This RNA response phenomenon appears biologically distinct from the classically defined response to dsRNA. RNA-transfected APC also polarize T cells in an IL-12-dependent manner toward the IFN-gamma(high)IL-5 (low) Th1 phenotype, suggesting a link between the detection of appropriately structured RNA and the skewing of immune responses toward those best suited for controlling intracellular microbes. RNA structured to emulate bacterial patterns constitutes a novel vaccine strategy to engender polarized Th1-type immune responses.
Koski
Gary K
GK
Harrison Department of Surgical Research, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA. dendritic_cell@hotmail.com
Karikó
Katalin
K
Xu
Shuwen
S
Weissman
Drew
D
Cohen
Peter A
PA
Czerniecki
Brian J
BJ
D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000469:parasitology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007114:Immunization / Q000379:methods; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000469:parasitology; D011061:Poly A / Q000378:metabolism; D012329:RNA, Bacterial / Q000737:chemistry* / Q000276:immunology*; D012330:RNA, Double-Stranded / Q000276:immunology / Q000502:physiology; D012333:RNA, Messenger / Q000737:chemistry / Q000276:immunology; D016053:RNA, Protozoan / Q000737:chemistry* / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology
D020413:3' Untranslated Regions; D012329:RNA, Bacterial; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D016053:RNA, Protozoan; D018664:Interleukin-12; D011061:Poly A