The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8
Abstract
Double-stranded ribonucleic acid (dsRNA) serves as a danger signal associated with viral infection and leads to stimulation of innate immune cells. In contrast, the immunostimulatory potential of single-stranded RNA (ssRNA) is poorly understood and innate immune receptors for ssRNA are unknown. We report that guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from human immunodeficiency virus-1 (HIV-1) stimulate dendritic cells (DC) and macrophages to secrete interferon-alpha and proinflammatory, as well as regulatory, cytokines. By using Toll-like receptor (TLR)-deficient mice and genetic complementation, we show that murine TLR7 and human TLR8 mediate species-specific recognition of GU-rich ssRNA. These data suggest that ssRNA represents a physiological ligand for TLR7 and TLR8.
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In the citing paper
“However, several RNA structural features have been described as immunostimulatory due to interactions with various RNA sensors such as Toll-like receptors, RIG-I, and PKR.”
From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [9]
In the citing paper
“TLR7 and TLR8 sense specific sequence motifs present in viral and endogenous single-stranded RNA (ssRNA), including microRNA (miRNA) [5, 6].”
From Neurodegenerative disease-associated microRNAs acting as signaling molecules modulate CNS neuron structure and viability (2025) · cites this paper as [6]
In the citing paper
“In contrast to microglia and macrophages, whose response to extracellular miRNA requires complexation with cationic lipids [4, 6, 20], cortical neurons internalized miRNA without transfection.”
From Neurodegenerative disease-associated microRNAs acting as signaling molecules modulate CNS neuron structure and viability (2025) · cites this paper as [6]
In the citing paper
“The optimization of mRNA constructs, including the coding sequence, can regulate immunogenicity without incorporation of modified nucleosides.”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [122]
In the citing paper
“Uridine depletion to reduce counterproductive immune reactions can be achieved by the replacement of uridine by codon optimization, but this must be balanced with regard to transfer RNA abundance.120, 121, 122”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [122]
Citations
Cites
A Toll-like receptor recognizes bacterial DNA
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Self-citationTakeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143
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
Small anti-viral compounds activate immune cells via the TLR7 MyD88–dependent signaling pathway
Hemmi, H., Kaisho, T., Takeuchi, O., Sato, S., Sanjo, H., Hoshino, K., Horiuchi, T., Tomizawa, H., Takeda, K., & Akira, S. (2002) · Nature Immunology · doi:10.1038/ni758 · Cited by 2,577
Self-citationAntigen Presentation and T Cell Stimulation by Dendritic Cells
Guermonprez, P., Valladeau‐Guilemond, J., Zitvogel, L., Théry, C., & Amigorena, S. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.100301.064828 · Cited by 1,990
Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors
Leadbetter, E. A., Rifkin, I. R., Hohlbaum, A. M., Beaudette-Zlatanova, B. C., Shlomchik, M. J., & Marshak‐Rothstein, A. (2002) · Nature · doi:10.1038/416603a · Cited by 1,929
Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition
Bauer, S., Kirschning, C. J., Häcker, H., Redecke, V., Hausmann, S., Akira, S., Wagner, H., & Lipford, G. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161293498 · Cited by 1,527
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Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells
Lund, J. M., Sato, A., Akira, S., Medzhitov, R. M., & Iwasaki, A. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030162 · Cited by 1,197
Self-citationDendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo.
Boczkowski, D., Nair, S. K., Snyder, D., & Gilboa, E. (1996) · The Journal of experimental medicine · doi:10.1084/jem.184.2.465 · Cited by 915
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- X. Du, A. Poltorak, Y. Wei, B. Beutler, Eur. Cytokine Netw.11, 362 (2000).
- T. H. Chuang, R. J. Ulevitch, Eur. Cytokine Netw.11, 372 (2000).
Cited by
Sorted by citations
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312
Self-citationToll-like receptors in innate immunity
Takeda, K. (2004) · International Immunology · doi:10.1093/intimm/dxh186 · Cited by 3,328
Karikó, K., Buckstein, M., Ni, H., & Weissman, D. (2005) · Immunity · doi:10.1016/j.immuni.2005.06.008 · Cited by 2,728
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
Self-citationmRNA-based therapeutics--developing a new class of drugs
Sahin, U., Karikó, K., & Türeci, Ö. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4278 · Cited by 2,474
Metadata
- Authors
- Heil, F., Hemmi, H., Hochrein, H., Ampenberger, F., Kirschning, C., Akira, S., Lipford, G., Wagner, H., & Bauer, S.
- Affiliations
- Japan Science and Technology Agency (JP)
- Corresponding author
- Heil, Florian
- Hemmi, Hiroaki
- Bauer, Stefan
- Venue
- Science
- Published
- 2004-03-05
- Volume
- 303
- Issue
- 5663
- Pages
- 1526-1529
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1969072247
- Cited by
- 3,947
- References
- 23
- Citations by year
- 2026: 95 · 2025: 99 · 2024: 138 · 2023: 137 · 2022: 166 · 2021: 200 · 2020: 154 · 2019: 127 · 2018: 150 · 2017: 146 · 2016: 161 · 2015: 142 · 2014: 169 · 2013: 174 · 2012: 174
- FWCI
- 104.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- single-stranded RNA, TLR7, TLR8, innate immunity, dendritic cells, macrophages, interferon-alpha, cytokine production, HIV-1 RNA, TLR ligands, species-specific recognition
- MeSH terms
- Quaternary Ammonium Compounds, Animals, Antigens, Differentiation, Base Sequence, Dendritic Cells, Fatty Acids, Monounsaturated, Genetic Complementation Test, Guanosine, Humans, Leukocytes, Mononuclear, Macrophages, Membrane Glycoproteins, Mice, Inbred C57BL, Oligoribonucleotides, Receptors, Cell Surface, Receptors, Immunologic, RNA, Viral, Species Specificity, Thionucleotides, Transfection, Uridine, HIV-1, Cytokines, Interferon-alpha, Adaptor Proteins, Signal Transducing, Toll-Like Receptors, Toll-Like Receptor 7, Toll-Like Receptor 8, Mice, Myeloid Differentiation Factor 88
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