RNA: DNA hybrids are a novel molecular pattern sensed by TLR9

• Rachel E Rigby ^[1] ; Lauren M Webb ^[3] ; Karen J Mackenzie ^[1] ; Yue Li ^[4] ; Andrea Leitch ^[1] ; Martin A M Reijns ^[1] ; Rachel J Lundie ^[1] ; Ailsa Revuelta ^[1] ; Donald J Davidson ^[1] ; Sandra Diebold ^[2] ; Yorgo Modis ^[4] ; Andrew S MacDonald ^[3] ; Andrew P Jackson ^[1]
  1. [1] University of Edinburgh

     University of Edinburgh

     Reino Unido

     
  2. [2] King's College London

     King's College London

     Reino Unido

     
  3. [3] 2 Institute of Immunology and Infection Research, University of Edinburgh Edinburgh, UK; ‡ Manchester Collaborative Centre for Inflammation Research, University of Manchester Manchester, UK
  4. [4] 3 Department of Molecular Biophysics and Biochemistry, Yale University New Haven, CT, USA

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 33, Nº. 6, 2014, págs. 542-558
• Idioma: inglés
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• Resumen

  • 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.