TY - JOUR
T1 - Cutting Edge
T2 - Innate Immune System Discriminates between RNA Containing Bacterial versus Eukaryotic Structural Features That Prime for High-Level, IL-12 Secretion by Dendritic Cells
AU - Koski, Gary K.
AU - Karikó, Katalin
AU - Xu, Shuwen
AU - Weissman, Drew
AU - Cohen, Peter A.
AU - Czerniecki, Brian J.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2004/4/1
Y1 - 2004/4/1
N2 - 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-γhigh IL-5low 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.
AB - 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-γhigh IL-5low 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.
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U2 - 10.4049/jimmunol.172.7.3989
DO - 10.4049/jimmunol.172.7.3989
M3 - Article
C2 - 15034009
AN - SCOPUS:1642268316
SN - 0022-1767
VL - 172
SP - 3989
EP - 3993
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -