Toll-like receptors in skin

Each TLR recognizes a different microbial component. TLR2 forms a heterodimer with TLR1 or TLR6 to recognize tri- and di-acyl lipopeptides, respectively. TLR4 recognizes LPS and TLR5 recognizes flagellin. These TLRs are located on the cell membrane and become internalized into phagosomes after interaction with their ligands. In contrast, TLR3 recognizes viral dsRNA, TLR7 and TLR8 recognize viral ssRNA, and TLR9 recognizes hypomethylated DNA (CpG motifs) of both bacteria and viruses and are located in intracellular membranes of endosomes and lysosomes. TLRs utilize MyD88 and TRIF adapters to initiate signaling. All TLRs except TLR3 can signal via MyD88. TLR2 and TLR4 also require the presence of TIRAP. MyD88 initiates a signaling cascade that eventually results in activation of NF-κB (and other pathways) to promote transcription of immunomodulatory genes. In contrast, TLR3 and TLR4 can also signal via TRIF in a MyD88-independent pathway. The TRIF pathway is critical in activating IRF3 (and IRF7), which promotes production of type I interferon (i.e. IFNα and IFNβ) and anti-viral immune responses.

Publication

Toll-like receptors in skin. () Lloyd S. Miller. Adv Dermatol. ;24:71-87. Figure: F2. Homo sapiens

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