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

Rachel E. Rigby, Lauren M Webb, Karen J. Mackenzie, Yue Li, Andrea Leitch, Martin A. M. Reijns, Rachel J. Lundie, Ailsa Revuelta, Donald Davidson, Sandra Diebold, Yorgo Modis, Andrew S. MacDonald, Andrew P. Jackson

• 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.