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

Gary K. Koski, Katalin Karikó, Shuwen Xu, Drew Weissman, Peter A. Cohen, Brian J. Czerniecki

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3989-3993
Number of pages5
JournalJournal of Immunology
Volume172
Issue number7
DOIs
StatePublished - Apr 1 2004

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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