Characterization of the Role of T Regulatory Cells in the Immune Response to Borrelia Burgdorferi Infection
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.
Available for download on Saturday, January 04, 2025