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

Toll-like receptors (TLRs) are a family of innate immune-recognition recept ors 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 prod uced by most viruses at some point during their replication(3). Here we sho w that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-kappaB and the production of type I interfero ns (IFNs). TLR3-deficient (TLR3(-/-)) mice showed reduced responses to poly inosine-polycytidylic acid (poly(I:C)), resistance to the lethal effect of poly(I:C) when sensitized with D-galactosamine (D-GalN), and reduced produc tion 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 cytokin e production through a signalling pathway dependent on MyD88. Moreover, pol y(I:C) can induce activation of NF-kappaB and mitogen-activated protein (MA P) kinases independently of MyD88, and cause dendritic cells to mature.