The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
RNA:DNA hybrids are a novel molecular pattern sensed by TLR9
Open accessAbstract
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. Nucleic acids are potent ligands for the pattern recognition receptors of the innate immune system. In this work, RNA:DNA hybrids are established to be a novel class of immunostimulatory nucleic acid, binding and activating intracellular TLR9 in dendritic cells. TLR9 may therefore have a wider role in host response to microbial infection, including the sensing of RNA:DNA hybrid replication intermediates. TLR9, classically known as cytokine‐inducing sensor of bacterial DNA, gains an additional role in detecting RNA:DNA hybrids containing virus‐derived sequences, making them a novel type of pathogen‐associated molecular pattern.
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Cites
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394
A Toll-like receptor recognizes bacterial DNA
Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., et al. (2000) · Nature · doi:10.1038/35047123 · Cited by 6,491 · cited 5×
“Intact RNA:DNA hybrids stimulate cytokine secretion by FLDCs Single-stranded DNA (ssDNA) can potently activate TLR9-mediated signalling (Hemmi et al , 2000), therefore the degradation of RNA:DNA hybrids by intracellular RNase H enzymes to ssDNA could provide an explanation for TLR9 activation by…”
InfluentialRecognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129
Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA
Diebold, S. S., Kaisho, T., Hemmi, H., Akira, S., & Reis e Sousa, C. (2004) · Science · doi:10.1126/science.1093616 · Cited by 3,444
IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K. J., Takeuchi, O., & Akira, S. (2005) · Nature Immunology · doi:10.1038/ni1243 · Cited by 2,562
Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide
Lande, R., Gregorio, J., Facchinetti, V., Chatterjee, B., Wang, Y.-H., Homey, B., Cao, W., Wang, Y.-H., Su, B., Nestle, F. O., et al. (2007) · Nature · doi:10.1038/nature06116 · Cited by 1,910
STING is a direct innate immune sensor of cyclic di-GMP
Burdette, D. L., Monroe, K. M., Sotelo-Troha, K., Iwig, J. S., Eckert, B., Hyodo, M., Hayakawa, Y., & Vance, R. E. (2011) · Nature · doi:10.1038/nature10429 · Cited by 1,570
Nucleic acid recognition by the innate immune system
Barbalat, R., Ewald, S. E., Mouchess, M. L., & Barton, G. M. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101340 · Cited by 577
Gall, A., Treuting, P., Elkon, K. B., Loo, Y.-M., Gale, M., Barber, G. N., & Stetson, D. B. (2012) · Immunity · doi:10.1016/j.immuni.2011.11.018 · Cited by 510
TLR13 Recognizes Bacterial 23 S rRNA Devoid of Erythromycin Resistance–Forming Modification
Oldenburg, M., Krüger, A., Ferstl, R., Kaufmann, A., Nees, G., Sigmund, A., Bathke, B., Lauterbach, H., Suter, M., Dreher, S., et al. (2012) · Science · doi:10.1126/science.1220363 · Cited by 405 · cited 1×
“Five TLRs sense nucleic acids: TLR3 (double-stranded RNA, dsRNA), TLR7/8 (single-stranded RNA, ssRNA), TLR9 (bacterial DNA) and TLR13 (23S rRNA) (Hemmi et al , 2000; Alexopoulou et al , 2001; Diebold et al , 2004; Heil et al , 2004; Oldenburg et al , 2012).”
Cited by
The cGAS-cGAMP-STING Pathway of Cytosolic DNA Sensing and Signaling
Cai, X., Chiu, Y.-H., & Chen, Z. J. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.040 · Cited by 988
Aicardi–Goutières syndrome and the type I interferonopathies
Crow, Y. J., & Manel, N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3850 · Cited by 925
Discriminating self from non-self in nucleic acid sensing
Schlee, M., & Hartmann, G. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.78 · Cited by 593
Recognition of Endogenous Nucleic Acids by the Innate Immune System
Roers, A., Hiller, B., & Hornung, V. (2016) · Immunity · doi:10.1016/j.immuni.2016.04.002 · Cited by 541
Cristini, A., Groh, M., Kristiansen, M. S., & Gromak, N. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.025 · Cited by 423
Metadata
- Authors
- Rigby, R. E., Webb, L. M., Mackenzie, K. J., Li, Y., Leitch, A., Reijns, M. A. M., Lundie, R. J., Revuelta, A., Davidson, D. J., Diebold, S., Modis, Y., MacDonald, A. S., & Jackson, A. P.
- Venue
- The EMBO Journal
- Published
- 2014-02-10
- Volume
- 33
- Issue
- 6
- Pages
- 542-558
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- OpenAlex
- W1982718713
- Cited by
- 162
- References
- 12
- FWCI
- 8.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Rigby, R. E., Webb, L. M., Mackenzie, K. J., Li, Y., Leitch, A., Reijns, M. A. M., Lundie, R. J., Revuelta, A., Davidson, D. J., Diebold, S., Modis, Y., MacDonald, A. S., & Jackson, A. P. (2014). RNA:DNA hybrids are a novel molecular pattern sensed by TLR9. The EMBO Journal. https://doi.org/10.1002/embj.201386117
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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