Localization of Borrelia burgdorferi in the nervous system and other organs in a nonhuman primate model of Lyme disease

Lyme borreliosis is caused by infection with the spirochete Borrelia burgdo rferi. Nonhuman primates inoculated with the N40 strain of B. burgdorferi d evelop infection of multiple tissues. including the central (CNS) and perip heral 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 Maca ca mulatta with 1 million spirochetes of the N40 strain of B. burgdorferi, and compared them with three infected immunocompetent animals acid two unin fected controls. The brain, spinal cord, peripheral nerves, skeletal muscle , heart, and bladder were obtained at necropsy 4 months later. The spiroche tal tissue load was first studied by polymerase chain reaction (PCR)-ELISA of the outer surface protein A (ospA) gene. Immunohistochemistry was used t o study the localization and numbers of spirochetes in tissues and the expr ession of spirochetal proteins and to characterize the inflammatory respons e. Hematoxylin and eosin and trichrome stains were used to study inflammati on and tissue injury. The results showed that the number of spirochetes was significantly higher in immunosuppressed animals. B. burgdorferi in the CN S localized to the leptomeninges, nerve roots, and dorsal root ganglia, but not to the parenchyma. Outside of the CNS, B. burgdorferi localized to end oneurium and to connective tissues of peripheral nerves, skeletal muscle, h eart, aorta, and bladder. Although ospA, ospB, ospC, and flagellin were pre sent at the time of inoculation, only flagellin was expressed by spirochete s in tissues 4 months later Significant inflammation occurred only in the h eart, and only immunosuppressed animals had cardiac fiber degeneration and necrosis. Plasma cells were abundant in inflammatory foci of steroid-treate d animals. We concluded that B. burgdorferi has a tropism for the meninges in the CNS and for connective tissues elsewhere in the body.