MURINE LYME BORRELIOSIS

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Lyme disease is a recently described spirochetal illness that is increasing in prevalence in many areas of the United States and Europe. Very little is known about basic issues such as susceptibility, latency, immunology, pathology, and pathogenesis. Our ignorance about these questions leads to uncertainty about optimal diagnosis and treatment. A reliable animal model is needed. The goal os this proposal is to investigate a mouse model of infection by Borrelia burgdorferi, the causative organism of Lyme disease, and to use the model to gain information on management, two major determinants of infection are B. burgdorferi strain and genetic background of the host. In this project the course of infection of a susceptible mouse strain by B. burgdorferi will be studied by investigating the influence of dose of organism, the route of injection, and day of sacrifice on culture positively and presence of bacteria and inflammation in organs. Cellular and humoral immune responses in infected mice will be assessed. Information gained in this initial characterization of the model can then be used to explore two important issues: genetically determined susceptibility in various mouse strains and variability in infectivity in different strains of the organism. The information gained from this work will improve our understanding of Lyme borreliosis by gaining information on the sequence of events after initial infection, the organs infected, changes in the spirochete as it remains in vivo, and pathological changes induced in the infection. These investigations will also aid in our understanding of the means by which B. burgdorferi is able to establish latency and evade, or at least make terms with, the host immune response.