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| Recognition of double-stranded RNA and activation of NF-kappa B by Toll-like receptor 3 |
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| Author(s): Alexopoulou L, Holt AC, Medzhitov R, Flavell RA |
| Source: NATURE Volume: 413 Issue: 6857 Pages: 732-738 Published: OCT 18 2001 |
| Times Cited: 1,907 References: 29 |
| 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(1,2). Double-stranded RNA (dsRNA) is a molecular pattern associated with viral infection, because it is produced by most viruses at some point during their replication(3). 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(1). 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Flavell, RA (reprint author), Immunobiol Sect, New Haven, CT 06520 USA |
Addresses:
1. Immunobiol Sect, New Haven, CT 06520 USA
2. Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA
3. Howard Hughes Med Inst, New Haven, CT 06520 USA
4. Yale Univ, Sch Med, New Haven, CT 06520 USA |
| Publisher: MACMILLAN PUBLISHERS LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 482ZK |
| ISSN: 0028-0836 |
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