Muzio M, Polentarutti N, Bosisio D, Manoj Kumar P P, Mantovani A
Department of Immunology and Cell Biology, Mario Negri Institute, via Eritrea 62, Milano, I-20157, Italy.
Biochem Soc Trans. 2000 Oct;28(5):563-6. doi: 10.1042/bst0280563.
Toll is a Drosophila gene essential for ontogenesis and anti-microbial resistance. Several orthologues of Toll have been identified and cloned in vertebrates, namely Toll-like receptors (TLRs). Human TLRs are a growing family of molecules involved in innate immunity. TLRs are characterized structurally by a cytoplasmic Toll/interleukin-1 receptor (TIR) domain and by extracellular leucine-rich repeats. TLRs characterized so far activate the MyD88/interleukin-1 receptor-associated kinase (IRAK) signalling pathway. Genetic, gene-transfer and dominant-negative approaches have involved TLR family members (TLR2 and TLR4) in Gram-positive and Gram-negative bacteria recognition and signalling. Accumulating evidence suggests that TLR2 is also involved in signalling-receptor complexes that recognize components of yeast and mycobacteria. However, the definitive roles of other TLRs are still lacking. A systematic approach has been used to determine whether different human leucocyte populations selectively or specifically express TLR mRNA. Based on expression pattern, TLR can be classified as ubiquitous (TLR1), restricted (TLR2, TLR4 and TLR5) and specific (TLR3). Expression and regulation of distinct but overlapping ligand-recognition patterns may underlie the existence of a large, seemingly redundant TLR family. Alternatively, the expression of a TLR in a single cell type may indicate a specific role for this molecule in a restricted setting.
Toll是果蝇中一个对个体发育和抗微生物抗性至关重要的基因。在脊椎动物中已鉴定并克隆出了Toll的几个直系同源物，即Toll样受体（TLR）。人类TLR是一个不断增加的参与天然免疫的分子家族。TLR在结构上的特征是具有一个胞质Toll/白细胞介素-1受体（TIR）结构域和细胞外富含亮氨酸的重复序列。到目前为止所鉴定的TLR激活MyD88/白细胞介素-1受体相关激酶（IRAK）信号通路。遗传学、基因转移和显性负性方法已将TLR家族成员（TLR2和TLR4）牵涉到革兰氏阳性和革兰氏阴性细菌的识别及信号传导中。越来越多的证据表明，TLR2也参与识别酵母和分枝杆菌成分的信号受体复合物。然而，其他TLR的确切作用仍然未知。已采用一种系统方法来确定不同人类白细胞群体是否选择性或特异性地表达TLR mRNA。根据表达模式，TLR可分为普遍存在的（TLR1）、受限的（TLR2、TLR4和TLR5）和特异的（TLR3）。不同但重叠的配体识别模式的表达和调控可能是庞大的、看似冗余的TLR家族存在的基础。或者，TLR在单一细胞类型中的表达可能表明该分子在受限环境中的特定作用。
