Delineating the requirement for the Borrelia burgdorferi virulence factor OspC in the mammalian host
Delineating the requirement for the Borrelia burgdorferi virulence factor OspC in the mammalian host
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DOI：
10.1128/iai.00158-06
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发表时间：
2006-06-01
影响因子：
3.1
通讯作者：
Rosa, Patricia A.
中科院分区：
文献类型：
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作者：
Stewart, Philip E.;Wang, Xiaohui;Rosa, Patricia A.
我们以前证明，外表面蛋白C（OspC的伯氏疏螺旋体是必不可少的建立哺乳动物感染。然而，OspC在哺乳动物感染中的作用尚不清楚。在这里，我们报告的实验设计，以区分两种模式的OspC功能在哺乳动物宿主：（i）OspC履行一个重要的生理作用的生长和宿主适应或（ii）OspC提供了一个保护作用，逃避先天免疫反应的组件。我们发现一个B。先前证明在免疫活性小鼠和SCH）小鼠中均无感染性的burgdorferiospC突变体可在植入大鼠腹膜内的透析膜室的相对免疫豁免环境中存活。ospC突变体也适应哺乳动物的环境，如由室培养的螺旋体的蛋白质谱所确定的。因此，OspC似乎没有为B的存活提供生理功能。哺乳动物宿主体内的伯氏螺旋体第二个模型，先天免疫系统的逃避，通过评估ospC突变体在骨髓分化蛋白88（MyD88）缺陷小鼠中的感染性来测试。最近的研究表明，B。通过MyD88依赖性信号传导途径阻止伯氏螺旋体在哺乳动物宿主中达到高细胞数。OspC突变体不能感染MyD88缺陷小鼠，这表明OspC的作用不能仅仅与MyD88介导的先天免疫的逃避有关。这些结果重申了OspC在哺乳动物感染中的重要性，并消除了这种神秘蛋白的简单功能模型。
We previously demonstrated that outer surface protein C (OspC of Borrelia burgdorferi is essential for establishing mammalian infection. However, the role of OspC in mammalian infection is unknown. Here, we report experiments designed to distinguish between two models of OspC function in the mammalian host: (i) OspC fulfills an essential physiological role for growth and host adaptation or (ii) OspC provides a protective role for evasion of components of the innate immune response. We found that a B. burgdorferi ospC mutant, previously demonstrated to be noninfectious in both immunocompetent and SCH) mice, could survive in the relatively immune-privileged environment of dialysis membrane chambers implanted within the peritoneum of a rat. The ospC mutant also adapts to the mammalian environment, as determined by the protein profiles of the chamber-cultivated spirochetes. Therefore, OspC does not appear to provide a physiological function for the survival of B. burgdorferi within the mammalian host. The second model, evasion of the innate immune system, was tested by assessing the infectivity of the ospC mutant in mice deficient for myeloid differentiation protein 88 (MyD88). Recent studies have shown that B. burgdorferi is prevented from reaching high cell numbers in the mammalian host by MyD88-dependent signaling pathways. The ospC mutant was incapable of infecting MyD88-deficient mice, suggesting that the role of OspC cannot be related solely to evasion of MyD88-mediated innate immunity. These results reiterate the importance of OspC in mammalian infection and eliminate simple models of function for this enigmatic protein.