Toll-like receptor 7 and Toll-like receptor 9 (TLR7 and TLR9)

Toll-like receptor 7 (TLR7) and Toll-like receptor 9 (TLR9) are endosomal pattern recognition receptors within the innate immune system, mainly recognizing viral single-stranded RNA (TLR7) and unmethylated CpG DNA motifs (TLR9) respectively. Both signal through the MyD88-dependent pathway, activate type I interferon and inflammatory responses, and play pivotal roles in immunity against infection, but are also key players in the development and exacerbation of autoimmune disorders such as SLE. They are structurally related, sharing features unique to the TLR7 subfamily, including a Z-loop in their extracellular domains. Therapeutically, both have been targeted by agonists for immune stimulation in cancer and infectious disease, and by antagonists to limit pathological inflammation in autoimmunity. Targeting these receptors remains challenging due to intricate cross-regulation, risk of excessive immune activation, and complex roles in disease pathogenesis.

Other names

TLR-7TLR-9Toll/interleukin-1 receptor 7Toll/interleukin-1 receptor 9CD287CD289Intracellular Toll-like receptors

Agonists: stimulate TLR7 or TLR9 to trigger an immune response via cytokine production (especially interferons), which can enhance anti-viral or anti-tumor immunity. Antagonists: inhibit TLR7/9 function to block pathological immune activation, primarily for autoimmune disease control. Indirect modulation: drugs like hydroxychloroquine impair receptor function by inhibiting endosomal acidification necessary for activation.