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The Journal of Immunology, 2004, 172: 3989-3993.
Copyright © 2004 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Innate Immune System Discriminates between RNA Containing Bacterial versus Eukaryotic Structural Features That Prime for High-Level IL-12 Secretion by Dendritic Cells1

Gary K. Koski2,*, Katalin Karikó{dagger}, Shuwen Xu*, Drew Weissman{ddagger}, Peter A. Cohen§ and Brian J. Czerniecki*

* Harrison Department of Surgical Research, Department of Surgery, {dagger} Department of Neurosurgery Research, and {ddagger} Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104; and § Center for Surgery Research, Cleveland Clinic Foundation, Cleveland, OH 44195

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}highIL-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.




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