Date of Award

Summer 2026

Language

English

Embargo Period

6-20-2026

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biomedical Sciences

Program

Biomedical Sciences

First Advisor

Nicholas Mantis

Committee Members

Nicholas Mantis, Katherine MacNamara, Kathleen McDonough

Keywords

Borrelia burgdorferi, tick, intradermal, BALB/c, MyD88

Subject Categories

Immunology and Infectious Disease

Abstract

Borrelia burgdorferi (Bb) is the causative agent of approximately 476,000 cases of Lyme disease in the United States and rising. Bb is spread through infected saliva of the black-legged tick, Ixodes scapularis, to the host. Patients infected with Bb experience short-term symptoms, such as erythema migrans (EMs), fatigue, pain, and cognitive impairment. If left untreated, Bb infection will cause long-term health complications, like Lyme neuroborreliosis and Lyme arthritis. It is postulated that symptoms associated with Lyme disease are driven in part by inflammation.

My thesis focuses on the skin as it holds significant immunological importance in the inflammatory response associated with Bb infection. The skin acts as a barrier between tissues and invading pathogens. When Bb enters the skin following a tick bite, it can alter the normal inflammatory response, assisting in its virulence. Inflammation is the effect of a signaling cascade, in which inflammatory cytokines and chemokines are secreted, resulting in the recruitment of immune cells to the site of inflammation. Bb can affect the functions of certain cytokines and impair pathways from performing cell-mediated destruction of the pathogen. I sought to determine if these inflammatory cytokines and chemokines can indicate early infection and disease progression in the host. In determining how these components play a role in infection, we will gain a better understanding of the process by which Bb is associated with inflammation.

In this thesis, I have studied the role inflammatory cytokines and chemokines play in early Bb infection. I have evaluated cytokine and chemokine concentrations post-Bb infection, and their concentrations at infection and dissemination sites within skin in both intradermal and tick challenges, utilizing a cytokine bead array assay. This study helped to better understand mechanistically how Bb and aspects of the innate immune system work to affect hosts’ inflammatory responses to infection. TLRs 1, 2, and 4 may play important roles in inflammatory kinetics and innate immune cell recruitment, especially with monocyte chemoattractant protein-1 (MCP-1). MCP-1 is important in macrophage and monocyte recruitment, which are important in phagocytosis of Bb. Furthermore, I studied the effect monoclonal antibodies LA-2 and B5 had on inflammatory cytokines and chemokines, where I observed they were able to suppress a response. In an attempt to determine the kinetics of MCP-1 signaling, I found that MyD88 was not specifically required for its expression.  Discoveries made in this study may aid in future therapies targeting cytokines or pathways controlled by these specific pro- and anti-inflammatory molecules, to facilitate more effective infection clearance.

License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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