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.
