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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.

SUBMITTER: Rigby RE

PROVIDER: S-EPMC3989650 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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

Rigby Rachel E RE Webb Lauren M LM Mackenzie Karen J KJ Li Yue Y Leitch Andrea A Reijns Martin A M MA Lundie Rachel J RJ Revuelta Ailsa A Davidson Donald J DJ Diebold Sandra S Modis Yorgo Y MacDonald Andrew S AS Jackson Andrew P AP

The EMBO journal 20140210 6

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 in ...[more]

PMID: 24514026

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