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 J Davidson; Sandra Diebold; Yorgo Modis; Andrew S MacDonald; Andrew P Jackson

doi:10.1002/embj.201386117

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 J Davidson, Sandra Diebold, Yorgo Modis, Andrew S MacDonald, Andrew P Jackson

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	542-558
Number of pages	17
Journal	EMBO Journal
Volume	33
Issue number	6
Early online date	21 Feb 2014
DOIs	https://doi.org/10.1002/embj.201386117
Publication status	Published - 18 Mar 2014

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embj.201386117.full
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2 Finished

Cathelicidins as immunomodulators of host defence against infectious diseases
Davidson, D.
MRC
1/04/11 → 31/03/17
Project: Research
Orchestration of the th2 response by dendritic cells
MacDonald, A.
MRC
1/05/08 → 31/10/13
Project: Research

Karen Mackenzie
- MRC Human Genetics Unit
- Deanery of Molecular, Genetic and Population Health Sciences - ECAT SCREDS Clinical Lecturer in Clinical Genetics
Person: Academic: Research Active

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title = "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.",

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

year = "2014",

month = mar,

day = "18",

doi = "10.1002/embj.201386117",

language = "English",

volume = "33",

pages = "542--558",

journal = "EMBO Journal",

issn = "0261-4189",

publisher = "Wiley-Blackwell",

number = "6",

}

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

In: EMBO Journal, Vol. 33, No. 6, 18.03.2014, p. 542-558.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - RNA:DNA hybrids are a novel molecular pattern sensed by TLR9

AU - Rigby, Rachel E

AU - Webb, Lauren M

AU - Mackenzie, Karen J

AU - Li, Yue

AU - Leitch, Andrea

AU - Reijns, Martin A M

AU - Lundie, Rachel J

AU - Revuelta, Ailsa

AU - Davidson, Donald J

AU - Diebold, Sandra

AU - Modis, Yorgo

AU - MacDonald, Andrew S

AU - Jackson, Andrew P

PY - 2014/3/18

Y1 - 2014/3/18

N2 - 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.

AB - 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.

U2 - 10.1002/embj.201386117

DO - 10.1002/embj.201386117

M3 - Article

VL - 33

SP - 542

EP - 558

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 6

ER -

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

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Cathelicidins as immunomodulators of host defence against infectious diseases

Orchestration of the th2 response by dendritic cells

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Karen Mackenzie

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