Heritable susceptibility to severe Borrelia burgdorferi-induced arthritis is dominant and is associated with persistence of large numbers of spirochetes in tissues.
Heritable susceptibility to severe Borrelia burgdorferi-induced arthritis is dominant and is associated with persistence of large numbers of spirochetes in tissues.
复制标题
对伯氏疏螺旋体引起的严重关节炎的遗传易感性占主导地位，并且与组织中大量螺旋体的持续存在有关。
DOI：
10.1128/iai.62.2.492-500.1994
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发表时间：
1994
影响因子：
3.1
通讯作者：
Weis,JJ
中科院分区：
文献类型：
--
作者：
Yang,L;Weis,JH;Eichwald,E;Kolbert,CP;Persing,DH;Weis,JJ
在人类莱姆病中，已观察到严重程度差别很大的症状。一种莱姆病小鼠模型已经开发出来，可以对接种伯氏疏螺旋体后出现轻度、中度和重度病变的小鼠进行分析。为了确定症状的差异是否反映了受感染组织中持续存在的螺旋体数量的差异，研究人员开发了一种敏感的PCR技术，可以在受感染小鼠的几乎任何组织中检测伯氏疏螺旋体DNA。该分析仅检测到三种螺旋体的DNA，发现早在感染后1周，严重关节炎C3H/HeJ小鼠的许多组织中就存在伯氏疏螺旋体DNA。虽然在脾脏、肝脏、大脑、肾脏、膀胱、子宫和淋巴结中也检测到伯氏疏螺旋体DNA，但心脏、耳朵和脚踝的感染尤其严重。相比之下，感染BALB/c小鼠的组织中检测到的螺旋体DNA水平要低得多，感染伯氏疏螺旋体后，BALB/c小鼠比C3H/HeJ小鼠患关节炎的程度要轻得多。这种差异在整个5周的分析中都很明显。竞争性PCR方法可以确定感染组织中螺旋体基因序列的绝对数量。来自C3H/HeJ小鼠的脚踝和心脏被发现含有10(7)个伯氏疏螺旋体ospA基因拷贝，而来自BALB/c小鼠的这些组织分别含有5倍和10倍的伯氏疏螺旋体DNA。通过感染C3H/HeJ与BALB/c小鼠的杂交后代，分析了严重病理的遗传调控。F1小鼠患上了严重的关节炎，并且在心脏和脚踝处含有高水平的疏螺旋体DNA，与C3H/HeJ亲本相似。这些发现表明，对严重关节炎的易感性是一个显性特征，并表明它可能与高水平的持续螺旋体有关。莱姆病的病理模型应考虑到病理的严重程度可能与感染组织中的生物体数量直接相关。
In human Lyme disease, symptoms with widely varying levels of severity have been observed. A mouse model of Lyme disease has been developed which allows analysis of mice with mild, moderate, and severe pathologies after inoculation with the spirochete Borrelia burgdorferi. To determine whether the differences in symptoms reflect differences in the number of spirochetes persisting in affected tissues, a sensitive PCR technique was developed to detect B. burgdorferi DNA in virtually any tissue of an infected mouse. This analysis, which detects DNA from as few as three spirochetes, revealed the presence of B. burgdorferi DNA in many tissues from severely arthritic C3H/HeJ mice as early as 1 week postinfection. The heart, ear, and ankle were particularly heavily infected, although B. burgdorferi DNA was also detected in spleen, liver, brain, kidney, bladder, uterus, and lymph nodes. In contrast, much lower levels of spirochete DNA were detected in tissues of infected BALB/c mice, which develop less severe arthritis when infected with B. burgdorferi than do C3H/HeJ mice. This difference was evident throughout the 5-week analysis. A competitive PCR method allowed determination of the absolute number of spirochete gene sequences in infected tissues. Ankles and hearts from C3H/HeJ mice were found to harbor 10(7) copies of the B. burgdorferi ospA gene, while these tissues from BALB/c mice contained 5- and 10-fold less B. burgdorferi DNA, respectively. The genetic regulation of severe pathology was analyzed by infecting the offspring of a cross between C3H/HeJ and BALB/c mice. The F1 mice developed severe arthritis and contained high levels of Borrelia DNA in the heart and ankle, similar to the C3H/HeJ parent. These findings indicate that susceptibility to severe arthritis is a dominant trait and suggest that it may correlate with high levels of persisting spirochetes. Models of pathology in Lyme disease should take into consideration the fact that severity of pathology may be directly related to the number of organisms in infected tissues.