Toll-like receptor 3 and Toll-like receptor 9 (TLR3 and TLR9)

Toll-like receptor 3 and toll-like receptor 9 are innate pattern recognition receptors, both localized in endolysosomal compartments, that identify viral and other microbial nucleic acids—dsRNA for TLR3 and unmethylated CpG-DNA for TLR9. Both are type I transmembrane glycoproteins with extracellular leucine-rich repeat (LRR) ligand recognition domains and intracellular TIR signaling domains. Upon ligand engagement, TLR3 and TLR9 initiate signaling cascades—TLR3 exclusively via the TRIF-dependent pathway, leading to type I interferon and inflammatory cytokine production; TLR9 signals through MyD88, activating NFκB and IRF pathways. Both receptors are clinically validated targets for immune modulation, especially in oncology and antiviral therapies, but carry significant safety and specificity considerations due to their central roles in immune amplification.

Other names

Toll-like receptor 3 (TLR3)Toll-like receptor 9 (TLR9)TLRs (as a family, not specific)

Agonists activate TLR3 or TLR9, triggering an intracellular signaling cascade via TRIF (for TLR3) or MyD88 (for TLR9) adaptor proteins, resulting in production of pro-inflammatory cytokines and type I interferon. Immune adjuvants leverage TLR3/9 activation to enhance antigen presentation and anti-tumor immune response.