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首页> 外文期刊>Infection and immunity >Porphyromonas gingivalis Lipopolysaccharide Contains Multiple Lipid A Species That Functionally Interact with Both Toll-Like Receptors 2 and 4
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Porphyromonas gingivalis Lipopolysaccharide Contains Multiple Lipid A Species That Functionally Interact with Both Toll-Like Receptors 2 and 4

机译：牙龈卟啉单胞菌脂多糖包含多种脂类A物种，它们与收费受体2和4均在功能上相互作用。

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The innate host response to lipopolysaccharide (LPS) obtained from Porphyromonas gingivalis is unusual in that different studies have reported that it can be an agonist for Toll-like receptor 2 (TLR2) as well as an antagonist or agonist for TLR4. In this report it is shown that P. gingivalis LPS is highly heterogeneous, containing more lipid A species than previously described. In addition, purification of LPS can preferentially fractionate these lipid A species. It is shown that an LPS preparation enriched for lipid A species at m/z 1,435 and 1,450 activates human and mouse TLR2, TLR2 plus TLR1, and TLR4 in transiently transfected HEK 293 cells coexpressing membrane-associated CD14. The HEK cell experiments further demonstrated that cofactor MD-2 was required for functional engagement of TLR4 but not of TLR2 nor TLR2 plus TLR1. In addition, serum-soluble CD14 effectively transferred P. gingivalis LPS to TLR2 plus TLR1, but poorly to TLR4. Importantly, bone marrow cells obtained from TLR2?/? and TLR4?/? mice also responded to P. gingivalis LPS in a manor consistent with the HEK results, demonstrating that P. gingivalis LPS can utilize both TLR2 and TLR4. No response was observed from bone marrow cells obtained from TLR2 and TLR4 double-knockout mice, demonstrating that P. gingivalis LPS activation occurred exclusively through either TLR2 or TLR4. Although the biological significance of the different lipid A species found in P. gingivalis LPS preparations is not currently understood, it is proposed that the presence of multiple lipid A species contributes to cell activation through both TLR2 and TLR4.
机译：从牙龈卟啉单胞菌获得的对脂多糖（LPS）的先天宿主应答是不寻常的，因为不同的研究报道它既可以作为Toll样受体2（TLR2）的激动剂，又可以作为拮抗剂或激动剂用于TLR4。在此报告中显示 P。牙龈脂多糖高度异质，比以前描述的脂质A种类更多。另外，LPS的纯化可以优先分离这些脂质A物质。结果表明，在 m / z 1,435和1,450处富含脂类A的LPS制剂可在共表达膜相关CD14的瞬时转染的HEK 293细胞中激活人和小鼠TLR2，TLR2加TLR1和TLR4。 HEK细胞实验进一步证明辅助因子MD-2是TLR4功能接合所必需的，而TLR2或TLR2加TLR1则不需要。此外，可溶于血清的CD14有效转移了 P。齿龈炎脂多糖到TLR2加TLR1，但差到TLR4。重要的是，从TLR2 ？/？和TLR4 ？/？小鼠获得的骨髓细胞对 P也有反应。与HEK结果一致的牙龈脂多糖（LPS）表现出 P。牙龈脂多糖可以同时利用TLR2和TLR4。从TLR2和TLR4双敲除小鼠获得的骨髓细胞中未观察到反应，表明 P。牙龈脂多糖的激活仅通过TLR2或TLR4发生。尽管在 P中发现了不同脂质A物种的生物学意义。目前还不了解牙龈脂多糖制剂，有人认为存在多种脂质A有助于通过TLR2和TLR4活化细胞。

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