Structural Modifications of Bacterial Lipopolysaccharide that Facilitate Gram-Negative Bacteria Evasion of Host Innate Immunity.
Structural Modifications of Bacterial Lipopolysaccharide that Facilitate Gram-Negative Bacteria Evasion of Host Innate Immunity.
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DOI：
10.3389/fimmu.2013.00109
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发表时间：
2013
影响因子：
7.3
通讯作者：
Matsuura M
中科院分区：
文献类型：
--
作者：
Matsuura M
细菌脂多糖（LPS）是革兰氏阴性菌特有的细胞壁组分，是一种代表性的病原体相关分子模式，其允许哺乳动物细胞识别细菌入侵并触发先天免疫应答。LPS的多糖部分主要对细菌起保护作用，例如防止补体攻击或用常见宿主碳水化合物残基伪装。被称为脂质A的脂质部分被Toll样受体4（TLR 4）/MD-2复合物识别，该复合物转导用于激活宿主先天免疫的信号。脂质A的基本结构是被磷酸基和酰基取代的葡糖胺二糖。具有六个酰基的脂质A（六酰化形式）已被证明是TLR 4/MD-2复合物的强刺激剂。这种类型的脂质A在多种革兰氏阴性细菌中是保守的，并且这些细菌容易被宿主细胞识别以激活防御性先天免疫应答。在一些细菌物种中已经观察到脂质A结构修饰为酰化程度较低的形式，并且这些形式是TLR 4/MD-2复合物的不良刺激物。这种修饰被认为有助于细菌逃避宿主先天免疫，从而增强致病性。这一假设得到了鼠疫耶尔森氏菌LPS研究的支持，当细菌在27°C（载体跳蚤的温度）生长时，LPS含有六酰化脂质A，当细菌在37°C的人体温度下生长时，LPS转变为含有较少酰化的形式。脂质A的这种改变是在Y.从跳蚤到人类的鼠疫主要是由于这种细菌的毒力超过了其他毒力因子。在一些其他细菌物种中，如土拉弗朗西斯菌、幽门螺杆菌和牙龈卟啉单胞菌，也表明了酰化程度较低的脂质A形式的类似作用，预计将进行进一步的研究来探索这一概念。
Bacterial lipopolysaccharide (LPS), a cell wall component characteristic of Gram-negative bacteria, is a representative pathogen-associated molecular pattern that allows mammalian cells to recognize bacterial invasion and trigger innate immune responses. The polysaccharide moiety of LPS primary plays protective roles for bacteria such as prevention from complement attacks or camouflage with common host carbohydrate residues. The lipid moiety, termed lipid A, is recognized by the Toll-like receptor 4 (TLR4)/MD-2 complex, which transduces signals for activation of host innate immunity. The basic structure of lipid A is a glucosamine disaccharide substituted by phosphate groups and acyl groups. Lipid A with six acyl groups (hexa-acylated form) has been indicated to be a strong stimulator of the TLR4/MD-2 complex. This type of lipid A is conserved among a wide variety of Gram-negative bacteria, and those bacteria are easily recognized by host cells for activation of defensive innate immune responses. Modifications of the lipid A structure to less-acylated forms have been observed in some bacterial species, and those forms are poor stimulators of the TLR4/MD-2 complex. Such modifications are thought to facilitate bacterial evasion of host innate immunity, thereby enhancing pathogenicity. This hypothesis is supported by studies of Yersinia pestis LPS, which contains hexa-acylated lipid A when the bacterium grows at 27°C (the temperature of the vector flea), and shifts to contain less-acylated forms when grown at the human body temperature of 37°C. This alteration of lipid A forms following transmission of Y. pestis from fleas to humans contributes predominantly to the virulence of this bacterium over other virulence factors. A similar role for less-acylated lipid A forms has been indicated in some other bacterial species, such as Francisella tularensis, Helicobacter pylori, and Porphyromonas gingivalis, and further studies to explore this concept are expected.