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RNA : DNA hybrids are a novel molecular pattern sensed by TLR 9
Author(s) -
Rigby Rachel E,
Webb Lauren M,
Mackenzie Karen J,
Li Yue,
Leitch Andrea,
Reijns Martin A M,
Lundie Rachel J,
Revuelta Ailsa,
Davidson Donald J,
Diebold Sandra,
Modis Yorgo,
MacDonald Andrew S,
Jackson Andrew P
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/embj.201386117
Subject(s) - biology , innate immune system , rna , pattern recognition receptor , dna , nucleic acid , interferon , pathogen associated molecular pattern , tlr9 , immune system , microbiology and biotechnology , genetics , virology , gene , gene expression , dna methylation
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 TLR 9 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.