Toll-like Receptor 5 (D9O8Q) Rabbit mAb #13811

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.

Toll-like receptor 5 (TLR5) is a pattern recognition receptor (PRR) that specifically recognizes bacterial flagellin (15). TLR5 binds flagellin directly on its lateral surface in a symmetrical arrangement and forms a 2/2 complex (16). TLR5 is expressed in epithelial cells, monocytes, and dendritic cells (DCs). TLR5 is an essential component of intestinal immunity at the mucosal barrier. It mediates immune tolerance to symbiotic flagellin during homeostasis and can lead to the production of chemokines and inflammatory cytokines when homeostasis is broken (17). The TLR5-microbiota axis is being investigated for prognostic and treatment potential of inflammatory bowel disease, and TLR5 agonists are being investigated in combination with immune checkpoint therapy as a strategy to treat previously unresponsive cancer patients (17,18).