Date of Award
Master of Science
Dean T Nardelli
Elizabeth Liedhegner, Jennifer Doll
Lyme disease, caused by Borrelia burgdorferi, is an increasingly important public health concern, with tens of thousands of new cases being diagnosed each year, even in previously non-endemic areas. It is known that symptoms of Lyme disease are caused by an inflammatory immune response initiated to aid in clearance of the pathogen. Left unchecked, these inflammatory responses can potentially increase tissue damage, leading to increased disease severity. Mechanisms responsible for the control of the inflammatory response to infection with B. burgdorferi are not entirely understood. Evidence exists that regulatory T (Treg) cells, a population of Foxp3-expressing CD4+ T cells known to play a vital role in controlling the immune response, may be important in reducing disease associated with B. burgdorferi infection. However, the role of Treg cells in host response to B. burgdorferi has not been examined fully. Here, we hypothesized that Treg cells control the development and progression of Lyme disease following B. burgdorferi infection. To test this hypothesis, two specific aims were addressed: (1) determine the effect of Treg cells on the development of arthritis following infection with B. burgdorferi; and (2) determine the effect of Treg cells on the control of the immune response following infection with B. burgdorferi. Using a mouse model that allows for specific depletion of Treg cells, we demonstrate that depletion of Treg cells immediately prior to infection with B. burgdorferi leads to significantly increased edema in the tibiotarsal joints of mice infected with a low dose of organisms. We also provide evidence that Treg cell depletion affects the ability of the immune system to prevent bacterial dissemination. Depletion of Treg cells appeared not to have an effect on the development of arthritis at the low doses of infection we used, despite the increased tibiotarsal joint swelling. Several weeks after infection, increased levels of IL-10 were observed in the serum of mice previously depleted of Treg cells. Collectively, these findings provide partial support for the hypothesis. Treg cell depletion prior to infection could potentially impact the induction of the initial immune response to B. burgdorferi, which could then have subsequent downstream effects on the development of disease; however, further studies are needed to test this hypothesis.
Nielsen, Kaitlyn, "Role of Regulatory T Cells in the Development and Progression of Lyme Disease in Balb/c Mice" (2019). Theses and Dissertations. 2411.
Available for download on Saturday, April 02, 2022