One of the most recent advances in immunology has been the identification and characterization of Toll like receptors (TLRs) that recognize microbial components and then activate specific innate and adaptive immune responses (see also Fast Breaking Comments by Dr. Shizuo Akira, August 2002). Our paper is probably highly cited because it falls in this fast breaking field of immunology, and describes for the first time that TLRs are involved not only in bacterial, but also in viral recognition.

The paper provides the first molecular characterization of how double-stranded RNA (dsRNA), a viral microbe, may activate the innate immune responses through TLR3 signaling.

Our study was initially performed with TLR3-knouckout mice that were produced by gene targeting with homologous recombination in embryonic stem cells, and the results were confirmed with in vitro transfection studies, using human TLR3. TLR3 confers responsiveness to poly (I: C) (a dsRNA analogue) and viral dsRNA, and affects downstream events such as activation of NF-kB, and production of inflammatory cytokines and type I IFNs.

TLRs tell the body that we have been infected. TLR3 does this for a virus infection. Understanding the mechanisms by which TLR3 recognize and activate antiviral immune responses is essential for the design of effective drugs against viruses.