Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo: exploration of the paradox of the early immune response to outer surface proteins A and C in Lyme disease.
Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo: exploration of the paradox of the early immune response to outer surface proteins A and C in Lyme disease.
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DOI：
10.1084/jem.183.1.261
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发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Bockenstedt LK
中科院分区：
文献类型：
--
作者：
Montgomery RR;Malawista SE;Feen KJ;Bockenstedt LK
伯氏疏螺旋体（莱姆病的病原体）的外表面蛋白 (Osps) 是针对该生物体的保护性免疫反应的主要目标。尽管培养的大多数北美伯氏疏螺旋体菌株都表达大量的 Osp A，但在自然感染患者或实验感染小鼠的血清中，该蛋白的抗体要么不存在，要么只检测到微弱。相比之下，Osp C 在培养的生物体上有不同的表达；引起早期强烈的体液反应。为了检验这一悖论，我们研究了伯氏疏螺旋体菌株 N40 克隆群体在实验性鼠疏螺旋体病早期过程中的体内适应情况。与人类疾病一样，在小鼠接种低剂量 (10(3)) 螺旋体后，Osp A 抗体仅微弱地存在于早期免疫库中。相比之下，Osp C 抗体很突出，尽管在培养的螺旋体上 Osp C mRNA 和蛋白质表达无法分别通过逆转录聚合酶链反应 (RT-PCR) 或间接免疫荧光检测到。这些观察结果促使我们研究 Osp A 和 Osp C 的体内表达。通过对未培养的螺旋体进行离体直接荧光染色和螺旋体 mRNA 的 PCR 扩增，我们表明 Osp C 确实在小鼠感染后由一些螺旋体表达。表达 Osp A 的螺旋体也可以在感染后 2 周内检测到，但在 30 天时则检测不到。 Osp A mRNA 虽然在感染第 14 天时存在，但在第 30 天时无法通过 RT-PCR 扩增，表明该 Osp 的表达是短暂的。这进一步意味着小鼠和人类中 Osp A 抗体的后期爆发可能是记忆性的。这些结果表明感染后螺旋体上的 Osp C 上调，或者表达 Osp C 的螺旋体在感染期间优先于表达 Osp A 的螺旋体扩增。这些结果对疫苗设计具有重要意义，并为 Osp A 抗体未能从感染宿主中根除螺旋体提供了一种解释。
The outer surface proteins (Osps) of Borrelia burgdorferi, the etiologic agent of Lyme disease, are principle targets of protective immune responses against this organism. Whereas most North American strains of B. burgdorferi in culture express an abundant amount of Osp A, antibodies to this protein are either absent or only weakly detected in the sera of naturally infected patients or experimentally infected mice. In contrast, Osp C, which has variable expression on cultured organisms; elicits an early, strong humoral response. To examine this paradox, we have studied the in vivo adaptation of a cloned population of B. burgdorferi strain N40 during the early course of experimental murine borreliosis. As in human disease, antibodies to Osp A were only weakly present in the early immune repertoire after murine inoculation with low dose (10(3)) spirochetes. In contrast, antibodies to Osp C were prominent, even though on cultured spirochetes Osp C mRNA and protein expression could not be detected by reverse transcription polymerase chain reaction (RT-PCR) or indirect immunofluorescence, respectively. These observations led us to investigate the expression of Osp A and Osp C in vivo. By direct fluorescent staining of uncultured spirochetes ex vivo and by PCR amplification of spirochetal mRNA, we show that Osp C is indeed expressed by some spirochetes after infection in the mouse. Spirochetes expressing Osp A could also be detected within the first 2 wk of infection, but not at 30 d. Osp A mRNA, although present at day 14 of infection, could not be amplified by RT-PCR at day 30, suggesting that the expression of this Osp is transient. This further implies that the late burst in Osp A antibodies in both mice and humans may be anamnestic. These results indicate that either Osp C is upregulated on spirochetes after infection, or Osp C- expressing spirochetes expand preferentially over those expressing Osp A during infection. These results have important implications for vaccine design and offer one explanation for the failure of Osp A antibodies to eradicate spirochetes from the infected host.
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影响因子：
6.4
作者：
FIKRIG, E;BOCKENSTEDT, LK;FLAVELL, RA
通讯作者：
FLAVELL, RA
影响因子：
4.4
作者：
GERN, L;RAIS, O;PETRE, J
通讯作者：
PETRE, J
影响因子：
3.1
作者：
MARGOLIS, N;ROSA, PA
通讯作者：
ROSA, PA
影响因子：
15.9
作者：
CRAFT, JE;FISCHER, DK;STEERE, AC
通讯作者：
STEERE, AC
DOI：
10.4269/ajtmh.1992.47.249
发表时间：
1992-08-01
影响因子：
3.3
作者：
ARMSTRONG, AL;BARTHOLD, SW;BECK, DS
通讯作者：
BECK, DS