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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.

Original publication

DOI

10.1002/embj.201386117

Type

Journal article

Journal

EMBO J

Publication Date

18/03/2014

Volume

33

Pages

542 - 558

Keywords

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