Phosphoryl moieties of lipid A from Neisseria meningitidis and N. gonorrhoeae lipooligosaccharides play an important role in activation of both MyD88- and TRIF-dependent TLR4-MD-2 signaling pathways.
Phosphoryl moieties of lipid A from Neisseria meningitidis and N. gonorrhoeae lipooligosaccharides play an important role in activation of both MyD88- and TRIF-dependent TLR4-MD-2 signaling pathways.
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DOI：
10.4049/jimmunol.1000953
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发表时间：
2010-12-01
期刊：
影响因子：
--
通讯作者：
Jarvis GA
中科院分区：
文献类型：
--
作者：
Liu M;John CM;Jarvis GA
我们之前已经证明，来自脑膜炎奈瑟菌和淋病奈瑟菌的低脂寡糖（LOS）与TLR4/MD-2复合物结合。在这项研究中，我们报道了来自不同脑膜炎球菌和淋球菌菌株的LOS具有不同的通过TLR4/MD-2激活NF-κB的能力，并且相对激活可以与MALDI-TOF质谱中的离子丰度相关，这表明了LOS的脂质A （LA）成分上的磷酸化取代基的数量。脑膜炎球菌菌株89I、淋球菌菌株1291和GC56对NF-κB的激活效力分别为高、中、低，它们通过TLR4/MD-2途径在单核细胞中不同程度地激活了细胞因子的表达。除了诱导典型的炎性细胞因子如TNF-α、IL-1β和IL-6外，与1291和GC56相比，在LA上磷基取代最多的89I LOS处理的细胞中，MIP-1α和MIP-1β也显著增加。我们发现LOS分别通过NF-κ b和IFN调节因子3 （IRF-3）转录因子激活MyD88和trif依赖通路。此外，LOS通过上调IRF-1诱导单核细胞表面共刺激分子CD80的表达。这些结果表明，来自脑膜炎奈瑟菌和淋病奈瑟菌LOS的LA磷酸化部分在MyD88-和trif -依赖途径的激活中发挥重要作用。我们的研究结果与细菌通过在LA上表达磷酸化片段来调节病原体相关分子模式以优化与宿主相互作用的概念一致。
We have previously shown that the lipooligosaccharide (LOS) from Neisseria meningitidis and N. gonorrhoeae engages the TLR4/MD-2 complex. In this study, we report that LOS from different meningococcal and gonococcal strains have different potencies to activate NF-κB through TLR4/MD-2, and that the relative activation can be correlated with ion abundances in MALDI-TOF mass spectrometry that are indicative of the number of phosphoryl substituents on the lipid A (LA) component of the LOS. The LOS from three of the strains, meningococcal strain 89I and gonococcal strains 1291 and GC56, representing high, intermediate and low potency on NF-κB activation, respectively, differently activated cytokine expression through the TLR4/MD-2 pathway in monocytes. In addition to induction of typical inflammatory cytokines such as TNF-α, IL-1β, and IL-6, MIP-1α and MIP-1β also were significantly higher in cells treated with 89I LOS which had the most phosphoryl substitutions on the LA compared to 1291 and GC56. We found that LOS activated both the MyD88- and TRIF-dependent pathways through NF-κB and IFN regulatory factor 3 (IRF-3) transcription factors, respectively. Moreover, LOS induced the expression of costimulatory molecule CD80 on the surface of monocytes via upregulation of IRF-1. These results suggest that phosphoryl moieties of LA from N. meningitidis and N. gonorrhoeae LOS play an important role in activation of both the MyD88- and TRIF-dependent pathways. Our findings are consistent with the concept that bacteria modulate pathogen-associated molecular patterns by expression of phosphoryl moieties on the LA to optimize interactions with the host.
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