Cadavid D, O'Neill T, Schaefer H, Pachner A R
Department of Neuroscience, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103, USA.
Lab Invest. 2000 Jul;80(7):1043-54. doi: 10.1038/labinvest.3780109.
Lyme borreliosis is caused by infection with the spirochete Borrelia burgdorferi. Nonhuman primates inoculated with the N40 strain of B. burgdorferi develop infection of multiple tissues, including the central (CNS) and peripheral nervous system. In immunocompetent nonhuman primates, spirochetes are present in low numbers in tissues. For this reason, it has been difficult to study their localization and changes in expression of surface proteins. To further investigate this, we inoculated four immunosuppressed adult Macaca mulatta with 1 million spirochetes of the N40 strain of B. burgdorferi, and compared them with three infected immunocompetent animals and two uninfected controls. The brain, spinal cord, peripheral nerves, skeletal muscle, heart, and bladder were obtained at necropsy 4 months later. The spirochetal tissue load was first studied by polymerase chain reaction (PCR)-ELISA of the outer surface protein A (ospA) gene. Immunohistochemistry was used to study the localization and numbers of spirochetes in tissues and the expression of spirochetal proteins and to characterize the inflammatory response. Hematoxylin and eosin and trichrome stains were used to study inflammation and tissue injury. The results showed that the number of spirochetes was significantly higher in immunosuppressed animals. B. burgdorferi in the CNS localized to the leptomeninges, nerve roots, and dorsal root ganglia, but not to the parenchyma. Outside of the CNS, B. burgdorferi localized to endoneurium and to connective tissues of peripheral nerves, skeletal muscle, heart, aorta, and bladder. Although ospA, ospB, ospC, and flagellin were present at the time of inoculation, only flagellin was expressed by spirochetes in tissues 4 months later. Significant inflammation occurred only in the heart, and only immunosuppressed animals had cardiac fiber degeneration and necrosis. Plasma cells were abundant in inflammatory foci of steroid-treated animals. We concluded that B. burgdorferi has a tropism for the meninges in the CNS and for connective tissues elsewhere in the body.
莱姆病螺旋体病由感染螺旋体伯氏疏螺旋体引起。用伯氏疏螺旋体N40菌株接种的非人灵长类动物会发生多个组织的感染，包括中枢（CNS）和外周神经系统。在免疫功能正常的非人灵长类动物中，组织中的螺旋体数量较少。因此，研究它们的定位和表面蛋白表达变化一直很困难。为了进一步研究这一点，我们给4只免疫抑制的成年恒河猴接种了100万个伯氏疏螺旋体N40菌株的螺旋体，并将它们与3只感染的免疫功能正常动物和2只未感染的对照进行比较。4个月后尸检时获取脑、脊髓、外周神经、骨骼肌、心脏和膀胱。首先通过外表面蛋白A（ospA）基因的聚合酶链反应（PCR）-ELISA研究螺旋体的组织负荷。免疫组织化学用于研究组织中螺旋体的定位和数量、螺旋体蛋白的表达，并表征炎症反应。苏木精和伊红以及三色染色用于研究炎症和组织损伤。结果表明，免疫抑制动物中的螺旋体数量明显更高。CNS中的伯氏疏螺旋体定位于软脑膜、神经根和背根神经节，但不定位于实质。在CNS之外，伯氏疏螺旋体定位于神经内膜以及外周神经、骨骼肌、心脏、主动脉和膀胱的结缔组织。虽然接种时存在ospA、ospB、ospC和鞭毛蛋白，但4个月后组织中的螺旋体仅表达鞭毛蛋白。仅在心脏中发生明显炎症，并且只有免疫抑制动物有心肌纤维变性和坏死。在类固醇治疗动物的炎症灶中浆细胞丰富。我们得出结论，伯氏疏螺旋体对CNS中的脑膜以及身体其他部位的结缔组织具有嗜性。
