Dissertation
DECIPHERING MECHANISMS OF VLSE-MEDIATED IMMUNE AVOIDANCE BY BORRELIA BURGDORFERI
Doctor of Philosophy (PhD), Washington State University
01/2014
Handle:
https://hdl.handle.net/2376/5402
Abstract
The current work has focused on antigenic variation of the VlsE surface lipoprotein, a key mechanism for immune evasion and persistent infection by the Lyme disease spirochete, Borrelia burgdorferi. The fact that only VlsE exhibits ongoing variation of its surface epitopes despite substantial numbers of other proteins expressed on the Borrelia burgdorferi surface suggests that spirochetes may utilize a VlsE-mediated system for immune avoidance of Borrelia burgdorferi surface antigens. The studies described in this dissertation have attempted to decipher whether such a system exists during murine infection by the Lyme pathogen, and the mechanism(s) behind this process. The data suggest that VlsE prevents recognition of Borrelia burgdorferi surface antigens from host antibodies. The work also explored VlsE involvement during reinfection and superinfection, and the potential immune barriers to secondary infection by Borrelia burgdorferi. As a result, innate immunity of the reservoir mouse host has been proposed to be a driving force for Borrelia burgdorferi heterogeneity during the enzootic cycle. The significance of this research is also reflected by the fact that findings, obtained from studies utilizing in vitro-grown or host-adapted Borrelia burgdorferi clones and laboratory strains of mice, were retested in the enzootic cycle model. This involved examination of the effects of vls mutation on persistent Borrelia burgdorferi infection of the natural reservoir, Peromyscus maniculatus, and acquisition and transmission by the tick vector, Ixodes scapularis. The findings highlight the significance of the vls system for long-term infection of the mammalian reservoir host and show that VlsE antigenic variability is advantageous for efficient tick acquisition of Borrelia burgdorferi from the infected murine hosts. Thus, the current work provides the most direct evidence of the importance of VlsE for the enzootic cycle of Lyme spirochetes, and underscores the significance of VlsE antigenic variation for maintaining the pathogen in nature. Finally, this work has also attempted to test a requirement of murine IgM for VlsE-mediated immune evasion by Borrelia burgdorferi during infection of mice. Overall, the present study represents a significant advance in our knowledge of immune evasion by Borrelia burgdorferi, and provides insight into the possible mechanisms involved in VlsE-mediated immune avoidance.
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Details
- Title
- DECIPHERING MECHANISMS OF VLSE-MEDIATED IMMUNE AVOIDANCE BY BORRELIA BURGDORFERI
- Creators
- Artem S. Rogovskyy
- Contributors
- Troy Bankhead (Advisor)Kelly A Brayton (Committee Member)Wendy C Brown (Committee Member)Susan Noh (Committee Member)Guy H Palmer (Committee Member)Glen A Scoles (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 181
- Identifiers
- 99900581842501842
- Language
- English
- Resource Type
- Dissertation