Toll-like receptor family and signalling pathway
Toll-like receptor family and signalling pathway
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DOI：
10.1042/bst0280563
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发表时间：
2000-10-01
影响因子：
3.9
通讯作者：
Mantovani, A
中科院分区：
文献类型：
--
作者：
Muzio, M;Polentarutti, N;Mantovani, A
Toll是果蝇的一种基因，对个体发育和抗微生物耐药是必不可少的。在脊椎动物中已经鉴定和克隆了几种Toll的同源基因，即Toll样受体(Toll-like Receptor，TLRs)。人类TLRs是一个日益增长的参与先天免疫的分子家族。TLRs的结构特征是胞内Toll/白细胞介素1受体(TIR)结构域和胞外富含亮氨酸的重复序列。目前鉴定的TLRs激活MyD88/白细胞介素1受体相关激酶(IRAK())信号通路。遗传、基因转移和显性-阴性方法涉及TLR家族成员(TLR2和TLR4)参与革兰氏阳性和革兰氏阴性细菌的识别和信号传递。越来越多的证据表明，TLR2还参与识别酵母和分枝杆菌成分的信号-受体复合体。然而，其他TLR的确切作用仍然缺乏。一种系统的方法已经被用来确定不同的人类白细胞群体是否选择性地或特异性地表达TLR mRNA。根据表达模式，TLR可分为泛发性(TLR1)、限制性(TLR2、TLR4和TLR5)和特异型(TLR3)。不同但重叠的配基识别模式的表达和调控可能是一个看似多余的大型TLR家族存在的基础。或者，TLR在单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。
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 Gramnegative 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.