The sole gateway to endotoxin response: how LPS was identified as Tlr4, and its role in innate immunity.
The sole gateway to endotoxin response: how LPS was identified as Tlr4, and its role in innate immunity.
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发表时间：
2001-04
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通讯作者：
Bruce Beutler;Alexander Poltorak
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作者：
Bruce Beutler;Alexander Poltorak
Tlr4 已成为细菌脂多糖 (LPS) 反应的特定通道。这种蛋白质存在的事实，以及它是单核细胞表达的蛋白质家族的成员之一的事实，使人们对吞噬细胞“看到”微生物宇宙的机制有了相当深入的了解。目前还不能假设所有 Tlrs 都具有与 Tlr4 相当的特异性，但考虑到所有蛋白质都受到分子限制，它们很可能确实如此。事实上，值得注意的是 Tlr4 能够感知如此多样化的 LPS 分子。 Tlr 蛋白的总数尚不清楚。虽然根据对果蝇基因的调查，可以预期大约有 30 种富含亮氨酸的蛋白质带有 Toll 样胞质结构域，但迄今为止，在哺乳动物中发现的 Toll 样基因要少得多，尽管现已归档了大约 200 万个表达序列标签序列，并且大部分基因组已被覆盖。事实上，一些 Toll 样蛋白是细胞因子受体。迄今为止，已报道了十种富含亮氨酸的 TLR。即使少量的受体也可能足以识别大多数病原体，无论是真菌、细菌还是原生动物。一些这样的受体也可能发挥发育作用。 Tlr 基因的单独突变删除和相互组合可能有助于确定这一新出现的蛋白质家族每个成员的功能。
Tlr4 has emerged as a specific conduit for the bacterial lipopolysaccharide (LPS) response. The fact that such a protein exists, and furthermore, the fact that it is one member of a family of proteins expressed by mononuclear cells, yields considerable insight into the mechanism by which phagocytes "see" the microbial universe. It cannot yet be assumed that all the Tlrs have specificity comparable to that of Tlr4, but it is probable that they do, given the molecular constraints to which all proteins are subject. Indeed, it is remarkable that Tlr4 is able to sense so diverse an array of LPS molecules as it does. The total number of Tlr proteins is not yet known. Although approximately 30 leucine-rich proteins bearing Toll-like cytoplasmic domains might be anticipated based on a survey of the genes in Drosophila, far fewer Toll-like genes have been found in mammals to date, although approximately 2 million expressed sequence tag sequences are now archived, and much of the genome has been covered. Some of the Toll-like proteins are, in fact, cytokine receptors. Ten leucine-rich Tlrs have been reported so far. Even a small number of receptors might be sufficient to confer recognition of most pathogens, be they fungi, bacteria, or protozoa. Some such receptors may also play developmental roles. The mutational deletion of Tlr genes alone and in combination with one another may help to establish the functions of each member of this newly emergent family of proteins.