Date of Award

December 2021

Degree Type

Thesis

Degree Name

Master of Science

Department

Biomedical Sciences

First Advisor

Dean Nardelli

Committee Members

Jennifer Doll, Elizabeth Liedhegner

Keywords

BALB/c, Borrelia, DEREG, IgG, Lyme, Regulatory T cells

Abstract

Lyme borreliosis, caused by the bacteria Borrelia burgdorferi, is the most common tick-borne disease in the United States. Difficulties and delays in diagnosing can leave patients with long-term illness affecting multiple body systems. Therefore, understanding the immunomodulatory mechanisms affecting disease pathology will aid in the development of therapeutics and/or a safe, effective vaccine. In this thesis, we aimed to test the hypothesis that depletion of regulatory T cells amplifies the humoral response to Borrelia burgdorferi but leads to worsened clinical manifestations. To test this hypothesis, “depletion of regulatory T cell” (“DEREG”) BALB/c mice were depleted of Treg cells prior to infection with B. burgdorferi and tibiotarsal joint swelling, histopathology, and IgG titers were assessed. The Treg cell-depleted DEREG mice that were infected trended towards having the greatest pathology in their tibiotarsal joint swelling measurements and histopathology scores, lending partial support to our central hypothesis. Additionally, to lay the foundation for future studies on the regulation of the memory humoral response to B. burgdorferi in a DEREG BALB/c model, we tested various vaccine doses in mice and challenged them with a homologous strain of B. burgdorferi three weeks later. We found that it would take a dose of at least 1x106 heat-inactivated organisms to induce a protective response capable of inhibiting immune cell infiltration in the tibiotarsal joints of wild-type BALB/c mice. While further studies are needed to better define the role of Treg cells in the humoral and protective memory responses to B. burgdorferi infection, this study adds partial support to the hypothesis that Treg cell depletion prior to infection with B. burgdorferi increases the clinical manifestations of disease

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