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

Author

Listed:
  • Lena Alexopoulou

    (Yale University School of Medicine)

  • Agnieszka Czopik Holt

    (Yale University School of Medicine
    Yale University School of Medicine)

  • Ruslan Medzhitov

    (Yale University School of Medicine
    Yale University School of Medicine)

  • Richard A. Flavell

    (Yale University School of Medicine
    Yale University School of Medicine)

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 responses1,2. Double-stranded RNA (dsRNA) is a molecular pattern associated with viral infection, because it is produced by most viruses at some point during their replication3. Here we show that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-κB 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 TLRs1. 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-κB and mitogen-activated protein (MAP) kinases independently of MyD88, and cause dendritic cells to mature.

Suggested Citation

  • Lena Alexopoulou & Agnieszka Czopik Holt & Ruslan Medzhitov & Richard A. Flavell, 2001. "Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3," Nature, Nature, vol. 413(6857), pages 732-738, October.
    • Handle: RePEc:nat:nature:v:413:y:2001:i:6857:d:10.1038_35099560
    DOI: 10.1038/35099560
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    Cited by:

    1. Chan Seok Lim & Yoon Ha Jang & Ga Young Lee & Gu Min Han & Hye Jin Jeong & Ji Won Kim & Jie-Oh Lee, 2022. "TLR3 forms a highly organized cluster when bound to a poly(I:C) RNA ligand," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. M. Clement & J. L. Forbester & M. Marsden & P. Sabberwal & M. S. Sommerville & D. Wellington & S. Dimonte & S. Clare & K. Harcourt & Z. Yin & L. Nobre & R. Antrobus & B. Jin & M. Chen & S. Makvandi-Ne, 2022. "IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Kentaro Sakaniwa & Akiko Fujimura & Takuma Shibata & Hideki Shigematsu & Toru Ekimoto & Masaki Yamamoto & Mitsunori Ikeguchi & Kensuke Miyake & Umeharu Ohto & Toshiyuki Shimizu, 2023. "TLR3 forms a laterally aligned multimeric complex along double-stranded RNA for efficient signal transduction," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    4. Friederike L. Pennemann & Assel Mussabekova & Christian Urban & Alexey Stukalov & Line Lykke Andersen & Vincent Grass & Teresa Maria Lavacca & Cathleen Holze & Lila Oubraham & Yasmine Benamrouche & En, 2021. "Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators," Nature Communications, Nature, vol. 12(1), pages 1-22, December.

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