| dc.description.abstract | Lyme disease (LD) is a tick-borne infection caused by Borrelia burgdorferi (Bb) that has a global impact and a high incidence in the United States. If not treated with antibiotics during the early stages of the disease within the first few weeks of infection, patients usually develop musculoskeletal symptoms and neurological complications that can include neurocognitive and neuropsychiatric manifestations. For many, regardless of the stage of the disease or duration of the infection, antibiotic treatment with oral or intravenous antibiotics is curative. Nevertheless, up to 20% of individuals that receive antibiotic treatment during late-stage infection do not find relief from their symptoms, despite multiple rounds of antibiotic therapy. Collectively, the symptoms that persist after antibiotic treatment are called Refractory Lyme arthritis (RLA) when symptoms are predominantly rheumatologic, or post-treatment Lyme Disease syndrome (PTLDS) when symptoms are predominantly neurologic, neuropsychiatric and/or neurocognitive. Neither of the syndromes is mutually exclusive. Currently there is no FDA approved treatment for PTLDS, and although autoimmune etiologies have been proposed, a definitive causal mechanism has not been identified.
A major limitation in our understanding of neurologic LD and its associated syndrome PTLDS is the lack of a suitable mouse model for modeling neurologic Bb infection. In section 1, we provide background on LD and summarize the hypotheses and approaches that we took in our research. In section 2, we review T cell and dendritic cell contributions to inflammation in RLA, to underscore what is known about complications of LD. Section 2 closes with a brief discussion of PTLDS and neuroborreliosis, to emphasize the questions that are currently understudied in LD. In section 3, we present a novel mouse model of neuroborreliosis that results from Bb infection of C3H/HeN mice, using the North American CSF-tropic strain of Bb, Bb 297, and an intradermal route of inoculation. We demonstrate that intradermal infection with Bb 297 results in persistent infection of the meninges and the brain, that CD4+ T cells accumulate in the brain during early and late-stage LD, and that both persistent infection and neuroimmune changes are temporally associated with significant behavioral deficits in nociception, mobility, and movement. In section 4 we provide a discussion of the implications of the research that we have performed. | en |
