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RNA:DNA hybrids are a novel molecular pattern sensed by TLR9 |
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| Authors: | Rachel E Rigby Yue Li Andrea Leitch Martin A M Reijns Rachel J Lundie Ailsa Revuelta Donald J Davidson Sandra Diebold Yorgo Modis Andrew S MacDonald Andrew P Jackson |
| Affiliation: | 1. MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Edinburgh, UK;2. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA;3. Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK;4. MRC Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK;5. Division of Immunology, Infection and Inflammatory Disease, King's College London, London, UK |
| 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. |
| Keywords: | innate immune signalling pathogen‐associated molecular pattern RNA:DNA hybrid TLR9 |