Cadavid Diego, Bai Yunhong, Dail Donna, Hurd Marie, Narayan Kavi, Hodzic Emir, Barthold Stephen W, Pachner Andrew R
Department of Neuroscience, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA.
Infect Immun. 2003 Dec;71(12):7087-98. doi: 10.1128/IAI.71.12.7087-7098.2003.
Lyme borreliosis is a multisystemic disease caused by various genospecies of the spirochete Borrelia burgdorferi. To investigate muscle involvement in the nonhuman primate (NHP) model of Lyme disease, 16 adult Macaca mulatta animals inoculated with strain N40 of B. burgdorferi sensu strictu by syringe or by tick bite or with strain Pbi of B. burgdorferi genospecies garinii by syringe were studied. Animals were necropsied while immunosuppressed on day 50 (two animals each inoculated with B. burgdorferi N40 by syringe and with B. garinii Pbi by syringe) or on day 90, 40 days after immunosuppression had been discontinued (four animals each inoculated with strain N40 by syringe, with strain N40 by tick bite, and with strain Pbi by syringe). Skeletal muscles removed at necropsy were studied by (i) microscopic examination of hematoxylin-eosin-stained sections for inflammation and tissue injury; (ii) immunohistochemical and digital image analyses for antibody and complement deposition and cellular inflammation; (iii) Western blot densitometry for the presence of antibodies; and (iv) reverse transcription-PCR for measurement of the spirochetal load or C1q (the first component of the complement cascade) synthesis. The results showed that N40 was more infectious for NHPs than Pbi. NHPs inoculated with N40 but not with Pbi developed myositis. The inflammation in skeletal muscle was more severe in NHPs inoculated with N40 by syringe than in those inoculated by tick bite. The predominant cells in the inflammatory infiltrate were T cells and plasma cells. The deposition of antibody and complement in inflamed muscles from N40-inoculated NHPs was significantly higher than that in Pbi-inoculated NHPs. The spirochetal load was very high in the two N40-inoculated NHPs examined while they were immunosuppressed but decreased to minimal levels in the NHPs when immunocompetence was restored. We conclude that myositis can be a prominent feature of Lyme borreliosis depending on the infecting organism and host immune status.
莱姆病是一种由伯氏疏螺旋体的多种基因种引起的多系统疾病。为了研究莱姆病非人灵长类动物（NHP）模型中的肌肉受累情况，我们对16只成年恒河猴进行了研究，这些动物通过注射器或蜱叮咬接种了严格意义上的伯氏疏螺旋体N40菌株，或通过注射器接种了伯氏疏螺旋体基因种伽氏疏螺旋体Pbi菌株。在第50天（两只通过注射器接种伯氏疏螺旋体N40和两只通过注射器接种伽氏疏螺旋体Pbi的动物）或在免疫抑制停止40天后的第90天（四只通过注射器接种N40菌株、四只通过蜱叮咬接种N40菌株和四只通过注射器接种Pbi菌株的动物）对动物进行尸检，此时动物处于免疫抑制状态。对尸检时取出的骨骼肌进行了以下研究：（i）对苏木精 - 伊红染色切片进行显微镜检查，以观察炎症和组织损伤；（ii）进行免疫组织化学和数字图像分析，以检测抗体和补体沉积以及细胞炎症；（iii）进行蛋白质印迹密度测定，以检测抗体的存在；（iv）进行逆转录 - PCR，以测量螺旋体载量或C1q（补体级联反应的第一成分）的合成。结果表明，N40对NHP的传染性比Pbi更强。接种N40而非Pbi的NHP发生了肌炎。通过注射器接种N40的NHP骨骼肌中的炎症比通过蜱叮咬接种的更严重。炎症浸润中的主要细胞是T细胞和浆细胞。接种N40的NHP发炎肌肉中的抗体和补体沉积明显高于接种Pbi的NHP。在两只接受检查的接种N40的NHP处于免疫抑制状态时，螺旋体载量非常高，但在免疫能力恢复时，NHP中的螺旋体载量降至最低水平。我们得出结论，根据感染的生物体和宿主免疫状态，肌炎可能是莱姆病的一个突出特征。
