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Description
The Toll-like receptor (TLR) family has recently emerged as key for sensing microbial infections and triggering inflammatory and innate responses. Ten TLRs have been cloned in humans. They share structural and functional homologies, as they are all able to detect micro-organisms through direct recognition of conserved Pathogen Associated Molecular Patterns (PAMPs) such as bacterial lipopolysaccharide (LPS) or viral double stranded RNA (dsRNA). Ligand recognition is mediated through the C-terminal Leucine Rich Repeat region, while signalling involves the N-terminal Toll/Interleukin-1 Receptor (TIR) domain. TLR3 has been identified as a receptor for dsRNA. Unlike other TLRs, the cytoplasmic tail of TLR3 does not contain a conserved proline residue, whose mutation confers LPS unresponsiveness in C3H/HeJ mice. TLR3 is the only TLR that signals exclusively through the TIR?containing adaptor TRIF (TIR?containing adaptor inducing IFNβ), which activates the transcription factors IRF3 and NFκB, and triggers type I interferon secretion. TLR3 is expressed in various cell types, such as fibroblasts, dendritic cells (DCs), or NK cells. While TLR3 is expressed at the cell surface in fibroblasts, it is mostly found in intracytoplasmic vesicles in DCs.