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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Several RNA structural features are immunostimulatory due to interactions with RNA sensors such as Toll-like receptors, RIG-I, and PKR.
“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]
Optimization of mRNA constructs, including the coding sequence, can regulate immunogenicity without incorporation of modified nucleosides.
“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]
Uridine depletion to reduce counterproductive immune reactions can be achieved by replacement of uridine by codon optimization, but this must be balanced with regard to transfer RNA abundance.
“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]
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- 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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