Human Toll-like receptor 4 recognizes host-specific LPS modifications
Human Toll-like receptor 4 recognizes host-specific LPS modifications
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DOI：
10.1038/ni777
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发表时间：
2002-04-01
影响因子：
30.5
通讯作者：
Miller, SI
中科院分区：
文献类型：
--
作者：
Hajjar, AM;Ernst, RK;Miller, SI
内毒素是革兰氏阴性细菌被膜的主要致炎成分，并被Toll样受体4(TLR4)-MD-2受体复合体识别。细菌可以改变其脂多糖的酰化状态，以响应环境的变化。一种机会细菌，铜绿假单胞菌，在适应囊性纤维化气道的过程中合成更高度酰化(六酰化)的脂多糖结构。在这里，我们表明人类，而不是小鼠，TLR4-MD-2识别这种适应，并传递强烈的促炎信号，以响应来自铜绿假单胞菌的六酰化而不是五酰化的脂多糖。虽然对脂质(IVA)和紫杉醇的反应依赖于小鼠MD-2，但铜绿假单胞菌内毒素结构的识别是由人TLR4的82个氨基酸区域介导的，该区域在物种之间是高度可变的。因此，与小鼠不同，人类使用TLR4识别细菌-宿主适应的分子信号，以调节先天免疫反应。
Lipopolysaccharide (LPS) is the principal proinflammatory component of the Gram-negative bacterial envelope and is recognized by the Toll-like receptor 4 (TLR4)-MD-2 receptor complex. Bacteria can alter the acylation state of their LPS in response to environmental changes. One opportunistic bacterium, Pseudomonas aeruginosa, synthesizes more highly acylated ( hexa-acylated) LPS structures during adaptation to the cystic fibrosis airway. Here we show that human, but not murine, TLR4-MD-2 recognizes this adaptation and transmits robust proinflammatory signals in response to hexa-acylated but not penta-acylated LPS from P. aeruginosa. Whereas responses to lipid(IVA) and taxol are dependent on murine MD-2, discrimination of P. aeruginosa LPS structures is mediated by an 82-amino-acid region of human TLR4 that is hypervariable across species. Thus, in contrast to mice, humans use TLR4 to recognize a molecular signature of bacterial-host adaptation to modulate the innate immune response.