Infection and inflammation in skeletal muscle from nonhuman primates infected with different genospecies of the Lyme disease spirochete Borrelia burgdorferi
Infection and inflammation in skeletal muscle from nonhuman primates infected with different genospecies of the Lyme disease spirochete Borrelia burgdorferi
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DOI：
10.1128/iai.71.12.7087-7098.2003
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发表时间：
2003-12-01
影响因子：
3.1
通讯作者：
Pachner, AR
中科院分区：
文献类型：
--
作者：
Cadavid, D;Bai, YH;Pachner, AR
莱姆病是由不同基因种的伯氏疏螺旋体引起的多系统疾病。为探讨莱姆病非人灵长类动物（NHP）模型的肌肉受累情况，对16只成年猕猴（Macaca mulatta）进行了注射、蜱叮咬和注射分别接种狭窄感伯氏疏螺旋体N40株和加力伯氏疏螺旋体Phi株的研究。免疫抑制动物在免疫抑制第50天（注射接种伯氏伯氏螺旋体N40和注射接种加里尼伯氏伯氏螺旋体Phi各2只动物）或免疫抑制停止后第90天（注射接种N40株、蜱叮咬接种N40株和注射接种Phi株各4只动物）进行尸检。解剖取下的骨骼肌通过(i)苏木精-伊红染色切片显微镜检查炎症和组织损伤；（ii）抗体、补体沉积和细胞炎症的免疫组化和数字图像分析；（iii） Western blot密度测定是否存在抗体；（iv）逆转录- pcr用于测量螺旋体负荷或C1q（补体级联的第一个组成部分）合成。结果表明，N40对NHPs的感染性大于Pbi。接种N40而不接种Phi的NHPs发生肌炎。注射接种N40的NHPs骨骼肌炎症反应比蜱叮咬接种N40的NHPs骨骼肌炎症反应严重。炎性浸润以T细胞和浆细胞为主。n40接种的NHPs在炎症肌肉中的抗体和补体沉积显著高于pbi接种的NHPs。在免疫抑制时，接种了n40的两种NHPs的螺旋体负荷非常高，但在免疫能力恢复后，螺旋体负荷降至最低水平。我们得出结论，肌炎可能是莱姆病的一个突出特征，这取决于感染的生物体和宿主的免疫状态。
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 Phi 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 Phi 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 Phi 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 Phi 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.