chapter  1
22 Pages

Assessing the Response of Cells to TLR Stimulation

ByKiyoshi Takeda, Masahiro Yamamoto, Kenya Honda

References ................................................................................................................ 17

Toll was first identified as an essential receptor for dorsoventral patterning in the developing embryo in Drosophila. In 1996, it was discovered that Drosophila Toll is involved in antifungal responses in the adult fly.1 Since then, the role of Toll receptors in the innate immune response has been studied intensively, not only in insects but also in mammals. This has led to the identification of Toll receptors in mammals, named Toll-like receptors (TLRs). The first mammalian homolog of Drosophila Toll was identified in 1997 as hToll (now termed TLR4).2 Subsequent studies have identified several proteins that are structurally related to TLR4. The TLR family now

comprises ten members in humans (TLR1-TLR10) and twelve in the mouse (TLR1TLR9 and TLR11-TLR13). The cytoplasmic portion of Toll-like receptors shows high similarity to that of the interleukin-1 (IL-1) receptor family, and is known as the Toll/IL-1 receptor (TIR) domain. Despite this similarity, the extracellular portions of both receptors are structurally unrelated. The IL-1 receptor is characterized by the presence of an Ig-like domain, whereas Toll-like receptors bear leucine-rich repeats in the extracellular domain.