TLRLiganden

TLRLiganden are molecules that bind Toll-like receptors (TLRs), a family of pattern recognition receptors that detect conserved microbial components and danger signals. They are expressed by many cell types, including dendritic cells, macrophages, and epithelial cells, and their engagement initiates innate immune responses that help shape adaptive immunity. TLR ligands include pathogen-associated patterns such as lipopolysaccharide recognized by TLR4, lipoproteins by TLR2/1 and TLR2/6, flagellin by TLR5, and nucleic acids such as CpG DNA by TLR9, double-stranded RNA by TLR3, and single-stranded RNA by TLR7/8, as well as danger signals released during tissue damage.

Recognition is compartmentalized: endosomal TLRs (TLR3, TLR7/8, TLR9) detect nucleic acids, while surface TLRs sense proteins and lipids. Signaling uses MyD88-dependent pathways for most TLRs and TRIF-dependent signaling for TLR3 and TLR4, triggering NF-κB, AP-1, and IRFs. This induces pro-inflammatory cytokines, chemokines, and type I interferons, and promotes dendritic cell maturation and T cell priming.

In clinical contexts, TLR ligands are explored as vaccine adjuvants and immunotherapies. Examples include MPLA, a TLR4 agonist used as an adjuvant, and CpG motifs targeting TLR9. Dysregulated TLR signaling is linked to inflammatory and autoimmune diseases, making TLRs attractive therapy targets and potential triggers of pathology.

Discovery: The TLR family was first identified in Drosophila; mammalian TLRs were characterized in the 1990s, establishing a central mechanism of innate immunity.