Toll-like Receptor 8 (D3Z6J) Rabbit mAb #11886

Members of the Toll-like receptor (TLR) family, named for the closely related Toll receptor in Drosophila, play a pivotal role in innate immune responses (1-4). TLRs recognize conserved motifs found in various pathogens and mediate defense responses (5-7). Triggering of the TLR pathway leads to the activation of NF-κB and subsequent regulation of immune and inflammatory genes (4). The TLRs and members of the IL-1 receptor family share a conserved stretch of approximately 200 amino acids known as the Toll/Interleukin-1 receptor (TIR) domain (1). Upon activation, TLRs associate with a number of cytoplasmic adapter proteins containing TIR domains, including myeloid differentiation factor 88 (MyD88), MyD88-adapter-like/TIR-associated protein (MAL/TIRAP), TIR domain-containing adapter-inducing IFN-β (TRIF), and Toll-receptor-associated molecule (TRAM) (8-10). This association leads to the recruitment and activation of IRAK1 and IRAK4, which form a complex with TRAF6 to activate TAK1 and IKK (8,11-14). Activation of IKK leads to the degradation of IκB, which normally maintains NF-κB in an inactive state by sequestering it in the cytoplasm.

TLR8 is an intracellular TLR localized to the endoplasmic reticulum, endosomes, lysosomes, and endolysosomes (4). It is activated by single-stranded viral RNA, as well as synthetic imidazoquinoline compounds including R-848 (5). TLR8 expression is highest in the lung and in myeloid cells (6,7). In addition, expression is upregulated by IFN-γ in monocyte-like leukemic THP-1 cells that have been differentiated with TPA (7).