The proposed research will develop and characterized a recently discovered rat model of Lyme disease; the first reproducible animal model of this important human illness. When LEW/N rats are inoculated with Borrelia burgdorferi, the causative agent of Lyme disease, they uniformly develop multisystemic infection and arthritis, the latter lesion being the most common and serious sequela of Lyme disease in man. Experiments described here will examine in inoculated rats, optimal conditions for inducing disease, the pathogenesis and duration of arthritis, immunological defenses during infection, whether other manifestations of Lyme disease occur, such as cutaneous, myoardial and neurological involvement, the virulence of B. burgdorferi obtained from different parts of the world, and the effect of genotype of susceptibility to disease. Studies will utilize a variety of techniques including: microbiological culture, histopathology, and immunohistochemistry to identify inflammatory cells, in vitro mitogenesis assays for cellular immunity, serological tests for antibody to B. burgdorferi and adoptive immunization. The role of T cells in lesion development and host defenses will require the use of athymic rats. Apart from the benefits these studies will have for Lyme disease research, they also after offer an opportunity to study a human-related arthritis for which the etiology is known.
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