Cited by 6,129Immune Response and InflammationNF-κB Signaling Pathwaysinterferon and immune responses

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Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3

Alexopoulou, Lena, Holt, Agnieszka Czopik, Medzhitov, Ruslan, Flavell, Richard A.·2001·Nature

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Abstract

Toll-like receptors (TLRs) are a family of innate immune-recognition receptors that recognize molecular patterns associated with microbial pathogens, and induce antimicrobial immune responses. Double-stranded RNA (dsRNA) is a molecular pattern associated with viral infection, because it is produced by most viruses at some point during their replication. Here we show that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-kappaB and the production of type I interferons (IFNs). TLR3-deficient (TLR3-/-) mice showed reduced responses to polyinosine-polycytidylic acid (poly(I:C)), resistance to the lethal effect of poly(I:C) when sensitized with d-galactosamine (d-GalN), and reduced production of inflammatory cytokines. MyD88 is an adaptor protein that is shared by all the known TLRs. When activated by poly(I:C), TLR3 induces cytokine production through a signalling pathway dependent on MyD88. Moreover, poly(I:C) can induce activation of NF-kappaB and mitogen-activated protein (MAP) kinases independently of MyD88, and cause dendritic cells to mature.

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Authors: Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A.
Affiliations: Yale University (US)
Howard Hughes Medical Institute (US)
Corresponding author: Medzhitov, Ruslan
Flavell, Richard A.
ORCID: Alexopoulou, Lena
Medzhitov, Ruslan
Flavell, Richard A.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2001-10
Volume: 413
Issue: 6857
Pages: 732-738
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/35099560
OpenAlex: W2076361525
Cited by: 6,129
References: 30
Citations by year: 2026: 134 · 2025: 156 · 2024: 161 · 2023: 174 · 2022: 203 · 2021: 270 · 2020: 216 · 2019: 203 · 2018: 209 · 2017: 209 · 2016: 219 · 2015: 237 · 2014: 258 · 2013: 279 · 2012: 303
FWCI: 66.43
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords: TLR3, double-stranded RNA, NF-κB activation, type I interferon, MyD88, poly(I:C), innate immunity, viral infection, MAPK signaling, dendritic cell maturation, inflammatory cytokines
MeSH terms: Amino Acid Sequence, Animals, Antigens, Differentiation, B-Lymphocytes, Cell Line, Cells, Cultured, Galactosamine, Humans, Interferon Type I, Lymphocyte Activation, Macrophages, Membrane Glycoproteins, Molecular Sequence Data, Poly I-C, Receptors, Cell Surface, Receptors, Immunologic, RNA, Double-Stranded, Virus Diseases, Signal Transduction, Cytokines, NF-kappa B, Sequence Homology, Amino Acid, Mitogen-Activated Protein Kinases, Drosophila Proteins, Adaptor Proteins, Signal Transducing, Toll-Like Receptors, Toll-Like Receptor 3, Mice, Myeloid Differentiation Factor 88

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Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3

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