RNA Mediated toll-like receptor stimulation in health and disease

Dalpke, Alexander H.; Helm, Mark

doi:10.4161/rna.20206

Cited by 113Immune Response and Inflammationinterferon and immune responsesInvertebrate Immune Response Mechanisms

RNA Mediated toll-like receptor stimulation in health and disease

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Dalpke, Alexander H., Helm, Mark·2012·RNA Biology

DOI 10.4161/rna.20206PMC PMC3495747

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Abstract

Besides their well known functions in storage and translation of information nucleic acids have emerged as a target of pattern recognition receptors that drive activation of innate immunity. Due to the paucity of building block monomers used in nucleic acids, discrimination of host and microbial nucleic acids as a means of self/foreign discrimination is a complicated task. Pattern recognition receptors rely on discrimination by sequence, structural features and spatial compartmentalization to differentiate microbial derived nucleic acids from host ones. Microbial nucleic acid detection is important for the sensing of infectious danger and initiating an immune response to microbial attack. Failures in the underlying recognitions systems can have severe consequences: thus, inefficient recognition of microbial nucleic acids may increase susceptibility to infectious diseases. On the other hand, excessive immune responses as a result of failed self/foreign discrimination are associated with autoimmune diseases. This review gives a general overview over the underlying concepts of nucleic acid sensing by Toll-like receptors. Within this general framework, we focus on bacterial RNA and synthetic RNA oligomers.

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Unmodified mRNA itself provides adjuvant activity through binding and activation of the innate immune sensors, mainly TLRs 3, 7, and 8.
“Unmodified mRNA itself provides adjuvant activity through binding and activation of the innate immune sensors, mainly TLRs 3, 7, and 8 (39).”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [39]
The section on posttranscriptional modifications reports that RNA activates TLR3, TLR7 and TLR8, and that certain modifications suppress this activation. The section on synthetic RNA identifies potential vaccine-adjuvant activity, but it discusses RNA oligonucleotides rather than establishing that unmodified mRNA itself provides adjuvant activity mainly through those three receptors. (LLM, conf=0.84)
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Authors: Dalpke, A. H., & Helm, M.
Affiliations: Heidelberg University (DE)
Johannes Gutenberg University Mainz (DE)
Corresponding author: Helm, Mark
ORCID: Dalpke, Alexander H.
Helm, Mark
Venue: RNA Biology
Publisher: Informa UK Limited
Published: 2012-06
Volume: 9
Issue: 6
Pages: 828-842
ISSN: 1547-6286 (ISSN-L)
1555-8584
DOI: 10.4161/rna.20206
PMC: PMC3495747
OpenAlex: W1994331999
Cited by: 113
References: 193
Citations by year: 2026: 4 · 2025: 13 · 2024: 5 · 2023: 16 · 2022: 16 · 2021: 12 · 2020: 13 · 2019: 9 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 2 · 2014: 2 · 2013: 5
FWCI: 0.27
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: RNA Biology (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
Keywords: Toll-like receptors, RNA sensing, pattern recognition receptors, innate immunity, bacterial RNA, nucleic acid recognition, autoimmune disease, infection susceptibility
MeSH terms: Animals, Autoimmune Diseases, Bacteria, Bacterial Infections, Base Sequence, DNA, Bacterial, Humans, Immunity, Innate, Nucleic Acid Conformation, Protein Binding, RNA, Bacterial, RNA, Small Interfering, Toll-Like Receptors

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