<p>This entry represents toll-like receptors confined to eukaryotes, which are key regulators of immune responses. Tol-like receptors are type-I transmembrane proteins with extracellular leucine-rich repeat (LRR) motifs and an intracellular Toll/interleukin-1 receptor (TIR) domain. Members of the TLR family contribute both to cell-cell interactions and to signalling, linking extracellular signals to specific gene-expression programmes [<cite idref="PUB00042888"/>]. Mammalian TLRs have essential roles in the direct recognition of infectious agents, initiating signalling through nuclear factor-kappa B (NF-kappaB), leading to the initiation of both innate and adaptive immune responses. Signalling by Toll-like receptors (TLRs) involves five adaptor proteins known as MyD88, MAL, TRIF, TRAM and SARM [<cite idref="PUB00042889"/>]. For example, TLR2 helps mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components, acting via MyD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response [<cite idref="PUB00042890"/>, <cite idref="PUB00042891"/>]. Genetic variations in TLR2 are associated with susceptibility to leprosy (OMIM:246300), a chronic disease associated with depressed cellular (but not humoral) immunity [<cite idref="PUB00042892"/>].</p> Toll-like receptor