IMMUNOLOGY TLR3 Tolls for dsRNA

Abstract: Members of the Toll-like receptor (TLR) family appear to recognize molecular patterns found on pathogens. Alexopoulou et al. have found that double-stranded RNA (dsRNA), which can be associate with viral infection, is recognized by TLR3. DsRNA-treated HEK293 cells that expressed TLR3 showed increased activity of the transcription factor NF-B. Murine TLR3^-/- bone marrow-derived macrophages (BMM) produced reduced amounts of cytokines in response to dsRNA treatment and had reduced NF-B activation compared with that in dsRNA-treated wild-type cells. Other experiments indicated that the intracellular proteins MyD88, IRAK, TRAF6, and Tollip, which function in other TLR family signaling pathways, also are essential for dsRNA-dependent TLR3 signaling. The expression of interferons (IFNs) and ß, which are important in the cellular response to viral infection, was reduced in dsRNA-treated tlr3^-/- mouse BMM cells, which suggests that responses to viruses producing dsRNA would be impaired in TLR3-deficient animals. Lysis of infected cells could liberate dsRNA that could activate TLR3 on nearby cells and increase their expression of IFN- and IFN-ß.

L. Alexopoulou, A. Czopik Holt, R. Medzhitov, R. A. Flavell, Recognition of double-stranded RNA and activation of NF-B by Toll-like receptor 3. Nature 413, 732-738 (2001). [Online Journal]