Borrelia burgdorferi-induced inflammation facilitates spirochete adaptation and variable major protein-like sequence locus recombination
Borrelia burgdorferi-induced inflammation facilitates spirochete adaptation and variable major protein-like sequence locus recombination
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DOI：
10.4049/jimmunol.167.6.3383
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发表时间：
2001-09-15
影响因子：
4.4
通讯作者：
Fikrig, E
中科院分区：
文献类型：
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作者：
Anguita, J;Thomas, V;Fikrig, E
螺旋体体内适应与伯氏疏螺旋体基因的优先表达有关。在本文中，我们证明，对感染伯氏疏螺旋体 N40 的 IFN-gammaR 缺陷型小鼠注射伯氏疏螺旋体免疫血清 4 天，可导致螺旋体清除。相反，免疫血清介导的伯氏疏螺旋体 N40 清除在免疫活性小鼠中并不明显，这表明 IFN-γ 介导的反应在伯氏疏螺旋体 N40 宿主适应中发挥作用。伯氏疏螺旋体免疫血清还可诱导已在体外传代 75 次的伯氏疏螺旋体 N40 的清除（伯氏疏螺旋体 N40-75），它是伯氏疏螺旋体 N40 的衍生物，在免疫功能正常的小鼠体内不能快速适应。伯氏疏螺旋体 N40-75 在小鼠体内产生的 IFN-γ 和 IL-12 水平低于伯氏疏螺旋体 N40，并且对伯氏疏螺旋体 N40-75 感染的小鼠施用这些细胞因子会导致螺旋体负荷增加，进一步表明 IFN-γ 介导的事件促进伯氏疏螺旋体存活。差异免疫筛选和RT-PCR证明，IFN-γ介导的信号促进螺旋体在可变主要蛋白样序列基因座（体内早期抗原变异的位点）处的重组，并且伯氏疏螺旋体N40在IFN-γR缺陷小鼠中的重组率低于对照动物。这些结果表明，小鼠免疫反应可以促进伯氏疏螺旋体的体内适应。
Spirochete adaptation in vivo is associated with preferential Borrelia burgdorferi gene expression. In this paper, we show that the administration of B. burgdorferi-immune sera to IFN-gammaR-deficient mice that have been infected with B. burgdorferi N40 for 4 days causes spirochete clearance. In contrast, immune sera-mediated clearance of B. burgdorferi N40 is not apparent in immunocompetent mice, suggesting a role for IFN-gamma -mediated responses in B. burgdorferi N40 host adaptation. B. burgdorferi-immune sera also induces clearance of B. burgdorferi N40 that have been passaged in vitro 75 times (B. burgdorferi N40-75), a derivative of B. burgdorferi N40 that does not rapidly adapt in vivo in immunocompetent mice. B. burgdorferi N40-75 produce lower levels of IFN-gamma and IL-12 in mice than does B. burgdorferi N40, and the administration of these cytokines to B. burgdorferi N40-75-infected mice results in an increased spirochetal burden, further indicating that IFN-gamma -mediated events promote B. burgdorferi survival. Differential immunoscreening and RT-PCR demonstrate that IFN-gamma -mediated signals facilitate spirochete recombination at the variable major protein like sequence locus, a site for early antigenic variation in vivo, and that recombination rates by B. burgdorferi N40 are lower in IFN-gammaR-deficient mice than in control animals. These results suggest that the murine immune response can promote the in vivo adaptation of B. burgdorferi.