Clearance of Borrelia burgdorferi may not be required for resistance to experimental Lyme arthritis

Clearance of Borrelia burgdorferi may not be required for resistance to experimental Lyme arthritis
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DOI:
10.1128/iai.66.5.2065-2071.1998
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发表时间:
1998-05-01
影响因子:
3.1
通讯作者:
Reiner, SL
Reiner, SL
中科院分区:
医学2区
文献类型:
--
作者:
Brown, CR;Reiner, SL

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近交系小鼠感染伯氏疏螺旋体可导致实验性莱姆关节炎的发生。关节炎的病理程度被认为与组织中螺旋体负荷的水平有关。为了进一步研究这一点,我们将抗性DBA/2(DBA)和敏感的C3H/HeJ(C3H)小鼠分别感染后足垫,观察21天的关节炎发展情况。为了定量测定组织中螺旋体的水平,我们创建了一个包含修饰的OspA和Fla基因片段的竞争性PCR分子。在整个实验期间,C3H小鼠患上了严重的胫踝关节关节炎,而DBA小鼠只出现了轻微的炎症。在第21天,当大体大小和组织学组成显示不同品系之间的关节炎有显著差异时,是否存在差异?竞争性聚合酶链式反应检测到的螺旋体DNA水平差异不大,21天的足踝组织培养物在C3H和DBA动物中也一致阳性,并且含有相对相似的螺旋体水平。这些结果表明,实验动物脚踝中螺旋体的存在不足以导致关节炎的发生。由于关节炎和非关节炎动物可以携带相对相同的螺旋体负荷,但保留了它们不同的表型结果,异常或过度活跃的免疫反应可能是关节炎易发小鼠的额外病理要求。
Infection of inbred mouse strains with Borrelia burgdorferi results in the development of experimental Lyme arthritis. The degree of arthritic pathology has been suggested to correlate with the level of spirochete burden within tissues. To investigate this further, we infected resistant DBA/2 (DBA) and susceptible C3H/HeJ (C3H) mice in the hind footpads and monitored arthritis development for 21 days. To quantitate levels of spirochetes within tissues, we created a competitive PCR molecule containing modified ospA and fla gene segments. C3H mice developed severe arthritis of the tibiotarsal joints, while DBA mice developed only mild inflammation throughout the experimental period. At day 21, when the gross size and histologic composition of ankles revealed significant differences in arthritis between the strains, there wa? little difference in levels of spirochete DNA as determined by competitive PCR, Cultures of ankle tissue at day 21 were also uniformly positive in both C3H and DBA animals and contained relatively similar levels of spirochetes. These results indicate that the presence of spirochetes in the ankles of experimental animals is not sufficient for arthritis development. Since arthritic and nonarthritic animals can harbor relatively equal spirochete burdens yet retain their distinct phenotypic outcomes, an aberrant or overly exuberant immune response may be an additional requirement for pathology in arthritis-prone mice.