The structurally similar, penta-acylated lipopolysaccharides of Porphyromonas gingivalis and Bacteroides elicit strikingly different innate immune responses.
The structurally similar, penta-acylated lipopolysaccharides of Porphyromonas gingivalis and Bacteroides elicit strikingly different innate immune responses.
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DOI：
10.1016/j.micpath.2009.04.015
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发表时间：
2009-08
影响因子：
3.8
通讯作者：
Darveau RP
中科院分区：
文献类型：
--
作者：
Berezow AB;Ernst RK;Coats SR;Braham PH;Karimi-Naser LM;Darveau RP
脂质A结构修饰可以显著影响宿主对细菌LPS的炎症反应。脆弱拟杆菌是一种与危及生命的脓毒症和腹腔内脓肿形成相关的机会致病菌，多形拟杆菌是一种对宿主肠组织正常发育至关重要的共生体，两者都产生由五酰化脂质A组成的免疫刺激性LPS。在限定的条件下，牙龈卟啉单胞菌（Porphyromonas gingivalis），一种与牙周炎相关的口腔病原体，也产生带有五酰化脂质A的LPS。然而，这种LPS制剂在刺激内皮细胞方面的效力比拟杆菌LPS低100-1000倍。我们使用MALDI-TOF MS和气相色谱分析了拟杆菌和牙龈卟啉单胞菌的脂质A结构，以确定这种现象的结构基础。尽管拟杆菌和牙龈卟啉单胞菌脂质A分子都是五酰化和单磷酸化的，但质量和脂肪酸含量的细微差异可以解释所观察到的LPS效力差异。这种脂肪酸异质性也是质谱中观察到的峰“簇”的原因，并混淆了LPS结构和免疫刺激能力之间的相关性。此外，我们表明拟杆菌和牙龈卟啉单胞菌LPS之间的效力差异是TLR 4依赖性的。总之，这些数据表明，脂质A结构的微妙变化可能会深刻影响宿主的先天免疫反应。
Lipid A structural modifications can substantially impact the host’s inflammatory response to bacterial LPS. Bacteroides fragilis, an opportunistic pathogen associated with life-threatening sepsis and intra-abdominal abscess formation, and Bacteroides thetaiotaomicron, a symbiont pivotal for proper host intestinal tissue development, both produce an immunostimulatory LPS comprised of penta-acylated lipid A. Under defined conditions, Porphyromonas gingivalis, an oral pathogen associated with periodontitis, also produces an LPS bearing a penta-acylated lipid A. However, this LPS preparation is 100–1000 times less potent than Bacteroides LPS in stimulating endothelial cells. We analyzed Bacteroides and P. gingivalis lipid A structures using MALDI-TOF MS and gas chromatography to determine the structural basis for this phenomenon. Even though both Bacteroides and P. gingivalis lipid A molecules are penta-acylated and mono-phosphorylated, subtle differences in mass and fatty acid content could account for the observed difference in LPS potency. This fatty acid heterogeneity is also responsible for the peak “clusters” observed in the mass spectra and obfuscates the correlation between LPS structure and immunostimulatory ability. Further, we show the difference in potency between Bacteroides and P. gingivalis LPS is TLR4-dependent. Altogether, the data suggest subtle changes in lipid A structure may profoundly impact the host’s innate immune response.
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影响因子：
10.8
作者：
Erridge, Clett;Spickett, Corinne M.;Webb, David J.
通讯作者：
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影响因子：
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作者：
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影响因子：
3.6
作者：
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通讯作者：
Miller, SI
影响因子：
3
作者：
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通讯作者：
Poxton, IR
影响因子：
3.1
作者：
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通讯作者：
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