Anguita J, Thomas V, Samanta S, Persinski R, Hernanz C, Barthold S W, Fikrig E
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
J Immunol. 2001 Sep 15;167(6):3383-90. doi: 10.4049/jimmunol.167.6.3383.
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.
体内螺旋体适应与伯氏疏螺旋体基因的优先表达相关。在本文中，我们表明，给感染伯氏疏螺旋体N40达4天的IFN-γR缺陷小鼠注射伯氏疏螺旋体免疫血清可导致螺旋体清除。相比之下，在免疫功能正常的小鼠中，免疫血清介导的伯氏疏螺旋体N40清除并不明显，这表明IFN-γ介导的反应在伯氏疏螺旋体N40宿主适应中起作用。伯氏疏螺旋体免疫血清还可诱导清除已在体外传代75次的伯氏疏螺旋体N40（伯氏疏螺旋体N40-75），伯氏疏螺旋体N40-75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。与伯氏疏螺旋体N40相比，伯氏疏螺旋体N40-75在小鼠体内产生的IFN-γ和IL-12水平较低，给感染伯氏疏螺旋体N40-75的小鼠注射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表明，IFN-γ介导的信号促进了可变主要蛋白样序列位点的螺旋体重组，该位点是体内早期抗原变异的位点，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，小鼠免疫反应可促进伯氏疏螺旋体的体内适应。
