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Nucleic acid agonists for Toll‐like receptor 7 are defined by the presence of uridine ribonucleotides
Open accessAbstract
Toll‐like receptor 7 (TLR7) mediates innate responses by responding to viral RNA in endocytic compartments. However, the molecular pattern recognised by TLR7 and whether it differs between RNA of viral and self origin remains unclear. Here, we identify nucleic acids that act as TLR7 agonists for mouse and human cells. We show that uridine and ribose, the two defining features of RNA, are both necessary and sufficient for TLR7 stimulation, and that short single‐stranded RNA (ssRNA) act as TLR7 agonists in a sequence‐independent manner as long as they contain several uridines in close proximity. Consistent with the notion that TLR7 lacks specificity for sequence motifs, we show that it is triggered equally efficiently by viral or self RNA delivered to endosomes. Our results support the notion that TLR7 recognises uracil repeats in RNA and that it discriminates between viral and self ligands on the basis of endosomal accessibility rather than sequence.
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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
Self-citationRecognition 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
CpG motifs in bacterial DNA trigger direct B-cell activation
Krieg, A. M., Yi, A.-K., Matson, S., Waldschmidt, T. J., Bishop, G. A., Teasdale, R., Koretzky, G. A., & Klinman, D. M. (1995) · Nature · doi:10.1038/374546a0 · Cited by 3,508
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
Karikó, K., Buckstein, M., Ni, H., & Weissman, D. (2005) · Immunity · doi:10.1016/j.immuni.2005.06.008 · Cited by 2,728
Innate immune recognition of viral infection
Kawai, T., & Akira, S. (2006) · Nature Immunology · doi:10.1038/ni1303 · Cited by 1,899
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Vaidyanathan, S., Azizian, K. T., Haque, A. K. M. A., Henderson, J. M., Hendel, A., Shore, S., Antony, J. S., Hogrefe, R. I., Kormann, M. S. D., Porteus, M. H., et al. (2018) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2018.06.010 · Cited by 262
“For example, it was reported that triplets of sequential uridines could activate TLR-7 and cause dendritic cells to release IFN-a.20 Likewise, RIG-I is reported to recognize uridine-rich sequences.25–28 Further research will be required to define the precise mechanism by which uridine depletion improves the activity o…”
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Metadata
- Authors
- Diebold, S. S., Massacrier, C., Akira, S., Paturel, C., Morel, Y., & Reis e Sousa, C.
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2006-11-27
- Volume
- 36
- Issue
- 12
- Pages
- 3256-3267
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2082192685
- Cited by
- 283
- References
- 6
- FWCI
- 7.45
- Type
- journal article
- Language
- en
- Open access
- bronze
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