Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3.
Journal:
Nature 2001 OctAuthors:
Alexopoulou L, Holt AC, Medzhitov R, Flavell RA
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
...[more] 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.[less]
Mesh Headings:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Antigens, Differentiation, B-Lymphocytes, Cell Line, Cells, Cultured, Cytokines, Drosophila Proteins, Galactosamine, Humans, Interferon Type I, Lymphocyte Activation, Macrophages, Membrane Glycoproteins, Mice, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Myeloid Differentiation Factor 88, NF-kappa B, Poly I-C, RNA, Double-Stranded, Receptors, Cell Surface, Receptors, Immunologic, Sequence Homology, Amino Acid, Signal Transduction, Toll-Like Receptor 3, Toll-Like Receptors, Virus Diseases