Functional consequences of toll-like receptor 4 polymorphisms
Functional consequences of toll-like receptor 4 polymorphisms
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DOI：
10.2119/2007-00135.ferwerda
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发表时间：
2008-05-01
影响因子：
5.7
通讯作者：
Netea, Mihai G.
中科院分区：
文献类型：
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作者：
Ferwerda, Bart;McCall, Matthew B. B.;Netea, Mihai G.
toll样受体4 （TLR4）是一种重要的病原体识别受体，主要识别革兰氏阴性菌的脂多糖（LPS），也可识别真菌和分枝杆菌病原体的结构以及内源性配体。TLR4的两个非同义多态性，Asp299Gly和Thr399IIe，已经被认为可以改变受体的功能。一些（但不是全部）研究表明，这些多态性导致细胞因子反应降低，并增加对革兰氏阴性感染的易感性。在这篇综述中，我们比较了评估Asp299Gly和Thr399IIe多态性对革兰氏阴性感染易感性影响的研究，并检查了这些多态性的表型后果。此外，我们回顾了TLR4多态性的地理分布，并提出了TLR4基因组成的进化压力模型。
Toll-like receptor 4 (TLR4) is an important pathogen recognition receptor that recognizes mainly lipopolysaccharide (LPS) of Gram-negative bacteria, but also structures from fungal and mycobacterial pathogens, as well as endogenous ligands. Two nonsynonymous polymorphisms of TLR4, Asp299Gly and Thr399IIe, have been suggested to alter the function of the receptor. Some, but not all, studies have proposed that these polymorphisms lead to reduced cytokine response and increased susceptibility to Gram-negative infections. In this review, we compare studies that assessed the effect of the Asp299Gly and Thr399IIe polymorphisms on susceptibility to Gram-negative infections and examine the phenotypic consequences of these polymorphisms. In addition, we review the geographical distribution of TLR4 polymorphisms and present a model for evolutionary pressures on the TLR4 genetic make-up.