Date of Award
Doctor of Philosophy
Elizabeth Liedhegner, Susan Cashin, Janis Eells
Borrelia burgdorferi, Immune regulation, Lyme Arthritis, Lyme Disease, Peripheral tolerance, T regulatory cells
Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common tick-borne infectious disease in the United States. The most common complication of Lyme disease is the development of Lyme arthritis. A dysregulated T cell immune response might contribute to Lyme arthritis development and persistence post-treatment in some patients. In addition, the host immune response may be incompetent in clearing the infection in some patients. Here, the hypothesis that T regulatory cells prevent Lyme arthritis development by containing T cell responses yet promote B. burgdorferi persistence by repressing the anti-pathogen immune response was tested. We show, using a Lyme arthritis-resistant mouse model, that T regulatory cells prevent Lyme arthritis development at various stages of Borrelia burgdorferi infection. Specifically, we demonstrate that T regulatory cell depletion before or after infection leads to tibiotarsal joint swelling and histopathology. We also provide evidence that T regulatory cells prevent Lyme arthritis by regulating pathogenic T helper 17 immune responses. Further, we demonstrate that T regulatory cells are involved in the humoral response to clear B. burgdorferi. We show that T regulatory cell depletion after infection increased B. burgdorferi-specific IgM antibodies and enhanced B. burgdorferi tissue clearance. However, T regulatory cell depletion after infection did not affect the generation of B. burgdorferi-specific IgG antibodies or the germinal centers. Our findings support and extend existing knowledge by demonstrating that T regulatory cells assist in restraining the T cell immune response to B. burgdorferi to prevent Lyme arthritis and that T regulatory cells may hinder the protective humoral immune response to B. burgdorferi and promote their survival.
Almatrook, Alaa, "Characterization of the Role of T Regulatory Cells in the Immune Response to Borrelia Burgdorferi Infection" (2022). Theses and Dissertations. 2976.
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