Degree Name
PhD (Doctor of Philosophy)
Program
Biomedical Sciences
Date of Award
8-2025
Committee Chair or Co-Chairs
Christopher Pritchett
Committee Members
Mariette Barbier, Laraine Powers, Tammy Ozment, Valentin Yakubenko
Abstract
Borrelia burgdorferi represents the most prevalent vector-borne bacteria in North America, affecting ~476,000 Americans annually yet persisting despite robust immune responses. This project reveals spirochetes target adaptive immunity through coordinated lymphatic colonization and precision immune dysregulation.
Using comparative host models (C57BL/6 vs. reservoir Peromyscus leucopus), we demonstrate lymph node colonization within 48-hours, with spirochetes exploiting LYVE-1-positive lymphatic structures as dissemination highways while avoiding the interior of follicular regions. Critically, we identify targeted CD4+ T-cell elimination in germinal center border zones at 21-DPI, precisely when these cells should be coordinating protective immunity. Concurrent upregulation of inhibitory receptor CD32b creates molecular stops preventing effective B-cell responses.
Reservoir hosts maintain immune integrity, revealing protective mechanisms absent in susceptible hosts. Multi-dose whole-cell vaccination preserves CD4+ populations and enhances antibody responses, demonstrating immune dysfunction can be circumvented.
These findings reframe Lyme pathogenesis: spirochetes convert immune networks into bacterial highways, and target regions of adaptive immunity.
Document Type
Dissertation - embargo
Recommended Citation
Land, Craig A., "Orchestrated Architecture Dismantling: Borrelia burgdorferi’s Coordinated Destruction of Adaptive Immune Responses" (2025). Electronic Theses and Dissertations. Paper 4579. https://dc.etsu.edu/etd/4579
Copyright
Copyright by the authors.
Included in
Disease Modeling Commons, Hemic and Lymphatic Diseases Commons, Immunology of Infectious Disease Commons, Pathogenic Microbiology Commons
