title: RNA:DNA hybrids are a novel molecular pattern sensed by TLR9.
abstract: 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.
authors: MRC Human Genetics Unit, MRC IGMM University of Edinburgh, Edinburgh, UK.
authors: Rachel E
authors: RE
authors: Rigby
authors: Lauren M
authors: LM
authors: Webb
authors: Karen J
authors: KJ
authors: Mackenzie
authors: Yue
authors: Y
authors: Li
authors: Andrea
authors: A
authors: Leitch
authors: Martin A M
authors: MA
authors: Reijns
authors: Rachel J
authors: RJ
authors: Lundie
authors: Ailsa
authors: A
authors: Revuelta
authors: Donald J
authors: DJ
authors: Davidson
authors: Sandra
authors: S
authors: Diebold
authors: Yorgo
authors: Y
authors: Modis
authors: Andrew S
authors: AS
authors: MacDonald
authors: Andrew P
authors: AP
authors: Jackson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D011992:Endosomes; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005454:Fluorescence Polarization; D005455:Fluorescent Antibody Technique; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D009692:Nucleic Acid Heteroduplexes / Q000276:immunology / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism*
chemical_list: D053594:Myeloid Differentiation Factor 88; D009692:Nucleic Acid Heteroduplexes; D051217:Toll-Like Receptor 9