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.