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

被引：128

作者：

Rigby, Rachel E. ^{[1
]}

Webb, Lauren M. ^{[2
]}

Mackenzie, Karen J. ^{[1
]}

Li, Yue ^{[3
]}

Leitch, Andrea ^{[1
]}

Reijns, Martin A. M. ^{[1
]}

Lundie, Rachel J. ^{[2
]}

Revuelta, Ailsa ^{[1
]}

Davidson, Donald J. ^{[4
]}

Diebold, Sandra ^{[5
]}

Modis, Yorgo ^{[3
]}

MacDonald, Andrew S. ^{[2
]}

Jackson, Andrew P. ^{[1
]}

机构：

[1] Univ Edinburgh, MRC IGMM, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland

[2] Univ Edinburgh, Inst Immunol & Infect Res, Edinburgh, Midlothian, Scotland

[3] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA

[4] Univ Edinburgh, Queens Med Res Inst, MRC Ctr Inflammat Res, Edinburgh, Midlothian, Scotland

[5] Kings Coll London, Div Immunol Infect & Inflammatory Dis, London, England

来源：

EMBO JOURNAL | 2014年 / 33卷 / 06期

基金：

欧洲研究理事会;

关键词：

innate immune signalling; pathogen-associated molecular pattern; RNA:DNA hybrid; TLR9; AICARDI-GOUTIERES-SYNDROME; PLASMACYTOID DENDRITIC CELLS; DOUBLE-STRANDED-RNA; TOLL-LIKE RECEPTORS; RIG-I; CPG-DNA; EXTRACELLULAR DNA; CUTTING EDGE; PLASMID DNA; RECOGNITION;

D O I：

10.1002/embj.201386117

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：542 / 558

页数：17

共 73 条

[31] A MULTISUBSTRATE ADDUCT INHIBITOR OF A PURINE BIOSYNTHETIC ENZYME WITH A PICOMOLAR DISSOCIATION-CONSTANT [J].