The sensing of nucleic acids by receptors of the innate immune system is a key component of antimicrobial immunity. RNA:DNA hybrids, as essential intracellular replication intermediates generated during infection, could therefore represent a class of previously uncharacterised pathogen-associated molecular patterns sensed by pattern recognition receptors. Here we establish that RNA:DNA hybrids containing viral-derived sequences efficiently induce pro-inflammatory cytokine and antiviral type I interferon production in dendritic cells. We demonstrate that MyD88-dependent signalling is essential for this cytokine response and identify TLR9 as a specific sensor of RNA:DNA hybrids. Hybrids therefore represent a novel molecular pattern sensed by the innate immune system and so could play an important role in host response to viruses and the pathogenesis of autoimmune disease.
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Animals, Blotting, Western, Dendritic Cells, Endosomes, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Fluorescence Polarization, Fluorescent Antibody Technique, Humans, Immunity, Innate, Immunoblotting, Mice, Mice, Inbred C57BL, Models, Immunological, Myeloid Differentiation Factor 88, Nucleic Acid Heteroduplexes, Real-Time Polymerase Chain Reaction, Signal Transduction, Toll-Like Receptor 9