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首页> 外文期刊>Infection and immunity >Bacteroides fragilis-Derived Lipopolysaccharide Produces Cell Activation and Lethal Toxicity via Toll-Like Receptor 4
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Bacteroides fragilis-Derived Lipopolysaccharide Produces Cell Activation and Lethal Toxicity via Toll-Like Receptor 4

机译：脆弱拟杆菌（Bacteroides fragilis）衍生的脂多糖通过Toll样受体4产生细胞活化和致命毒性。

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Bacteroides fragilis, which is part of the normal intestinal flora, is a frequent cause of serious disease, especially in diabetic and surgical patients. In these conditions, B. fragilis lipopolysaccharide (LPS) is likely to play a major pathophysiologic role. B. fragilis LPS is structurally different from classical enterobacterial LPS, whose biological activities are mediated by Toll-like receptor 4 (TLR4) activation. The ability of B. fragilis LPS to activate TLR4 and TLR2 was investigated here, since evidence on this issue is scarce and controversial. Each of four different protein-free B. fragilis LPS preparations could induce interleukin-8 responses in cells cotransfected with TLR4/CD14/MD2 but not TLR4/CD14 alone. Two of the preparations also induced cytokine production in cells cotransfected with TLR2/CD14 or in peritoneal macrophages from TLR4 mutant C3H/HeJ mice. Both of these activities, however, were lost after repurification with a modified phenol reextraction procedure. Importantly, all preparations could induce endotoxic shock in TLR2-deficient mice, but not in TLR4 mutant C3H/HeJ mice. Consistent with these findings, anti-TLR4 and anti-CD14, but not anti-TLR2, antibodies could inhibit B. fragilis LPS-induced cytokine production in human monocytes. Collectively, these results indicate that B. fragilis LPS signals via a TLR4/CD14/MD2-dependent pathway, and it is unable to activate TLR2. Moreover, our data document the occurrence of TLR2-activating contaminants even in highly purified B. fragilis LPS preparations. This may explain earlier contradictory findings on the ability of B. fragilis LPS to activate cells in the absence of functional TLR4. These data may be useful to devise strategies to prevent the pathophysiologic changes observed during B. fragilis sepsis and to better understand structure-activity relationships of LPS.
机译：属于正常肠道菌群的脆弱类杆菌是导致严重疾病的常见原因，尤其是在糖尿病和外科手术患者中。在这些情况下， B。脆弱的脂多糖（LPS）可能起主要的病理生理作用。 B。脆弱类脂多糖与经典肠杆菌脂多糖在结构上有所不同，后者的生物学活性是由Toll样受体4（TLR4）激活介导的。 B的能力。脆弱类脂多糖激活TLR4和TLR2的方法在这里进行了研究，因为有关该问题的证据很少且存在争议。四种不同的无蛋白B蛋白质中的每一种。易碎的脂多糖制剂可在与TLR4 / CD14 / MD2共转染的细胞中诱导白介素8的反应，而对单独的TLR4 / CD14则无影响。其中两种制剂还诱导了与TLR2 / CD14共转染的细胞或TLR4突变C3H / HeJ小鼠腹膜巨噬细胞中细胞因子的产生。但是，用改良的苯酚再萃取程序进行再纯化后，这两种活性都消失了。重要的是，所有制剂都可以在TLR2缺陷型小鼠中诱发内毒素性休克，但在TLR4突变体C3H / HeJ小鼠中则不能。与这些发现一致的是，抗TLR4和抗CD14抗体可以抑制 B，但不能抗TLR2。脆弱类脂多糖诱导人单核细胞产生细胞因子。这些结果共同表明 B。脆弱类脂多糖通过TLR4 / CD14 / MD2依赖性途径信号转导，无法激活TLR2。此外，我们的数据记录了即使在高度纯化的 B中也发生了TLR2活化污染物。脆弱的LPS制剂。这可能解释了早期关于B能力的矛盾发现。在没有功能性TLR4的情况下，脆弱类LPS可以激活细胞。这些数据可能有助于设计策略，以防止在B期观察到的病理生理变化。易碎败血症，以更好地了解脂多糖的构效关系。

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