Date of Award
December 2023
Degree Type
Thesis
Degree Name
Master of Science
Department
Biomedical Sciences
First Advisor
Dean Nardelli
Committee Members
Elizabeth Liedhegner, Troy Skowr
Abstract
Lyme disease, or Lyme borreliosis, is the most common vector-borne disease in North America. We recently showed, using “depletion of regulatory T cell” (“DEREG”) mice on the Lyme arthritis-resistant C57BL/6 background, that ablation of regulatory T (Treg) cells immediately prior to infection with Borrelia burgdorferi resulted in increased swelling and histopathology of the tibiotarsal joints that were not observed in Treg cell-sufficient mice. This pathology was evident two to three weeks after infection, well after the rebound of Treg cells in our model, suggesting that even a temporary decrease in the numbers of these cells at the time of infection was sufficient to establish a trajectory toward disease development several weeks later. However, the effects of Treg cells early in B. burgdorferi infection- specifically, those on spirochetal dissemination and cytokine responses- have not yet been examined. Complicating this investigation is the phenomenon that robust inflammatory responses may function to combat early infection but also contribute to the development of the ensuing disease. Here, we hypothesized that depletion of Treg cells in B. burgdorferi-infected C57BL/6 DEREG mice would lead to limited dissemination of the spirochete but also to an increased inflammatory cytokine response in the days following infection. Seven days after infection, we observed a significantly greater presence of spirochetes in the skin of the injection site and in ear tissues of mice that previously had been depleted of Treg cells than in Treg cell-sufficient mice. By contrast, we observed higher borrelial loads in the hearts, knee joints, and tibiotarsal joints of infected, Treg cell-sufficient mice than in Treg cell-depleted counterparts 7 days after infection. However, these increases were not statistically significant. Furthermore, we observed that splenocytes obtained 7 days after infection of Treg cell-depleted mice produced less IL-12 than did splenocytes from Treg-sufficient counterparts, and that the levels of several other cytokines did not differ between these groups. Taken together, our findings suggest that Treg cells may affect early borrelial dissemination and Th1-associated cytokine responses to the spirochete in certain ways that appear counterintuitive to these cells’ effects on pathology during established infection. Certain data either support or refute our hypothesis. The role of Treg cells in the host response to B. burgdorferi is not fully understood. Our findings may provide a unique insight into the early host response during B. burgdorferi infection.
Recommended Citation
anderson, phillip Nevin, "EFFECT OF REGULATORY T CELLS ON DISSEMINATION OF, AND IMMUNE RESPONSE TO, BORRELIA BURGDORFERI DURING EARLY INFECTION" (2023). Theses and Dissertations. 3388.
https://dc.uwm.edu/etd/3388