Date of Award

Spring 3-2023

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

School

Biological, Environmental, and Earth Sciences

Committee Chair

Dr. Shahid Karim

Committee Chair School

Biological, Environmental, and Earth Sciences

Committee Member 2

Dr. Fengwei Bai

Committee Member 2 School

Biological, Environmental, and Earth Sciences

Committee Member 3

Dr. Yanlin Guo

Committee Member 3 School

Biological, Environmental, and Earth Sciences

Committee Member 4

Dr. Sharah Morgan

Committee Member 4 School

Biological, Environmental, and Earth Sciences

Committee Member 5

Dr. Hao Xu

Committee Member 5 School

Biological, Environmental, and Earth Sciences

Abstract

Alpha-Gal Syndrome (AGS) is a delayed allergic reaction caused by specific IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (α-gal) present in red meat. AGS is a growing concern globally, with over 34,000 confirmed cases in the United States alone. Studies have linked AGS to tick bites, which sensitizes hosts against α-gal antigens and elevates α-gal specific IgE. This dissertation investigates the role of tick and host-associated factors in AGS development. Microbiome analysis of Am. americanum ticks revealed a comprehensive core microbiome profile and showed that new Fransiella-like endosymbionts dominate and outcompete conventional tick Coxiella endosymbionts. Ticks subjected to tetracycline treatment showed significant microbiome dysbiosis but had no impact on the tick's N-glycan machinery, indicating that tick microbiome dysbiosis does not affect N-glycan-associated α-gal development. Inhibiting tick N-glycan synthesis machinery and the galactosyltransferase enzyme using inhibitors resulted in a decrease in α-gal associated N-glycans, suggesting the tick's N-glycan machinery is crucial for α-gal development. RNA interference studies showed that the tick's enzyme α-D-galactosidase is vital in α-gal antigen synthesis in ticks, while the enzyme β-1,4GalT was not significantly associated with α-gal development. This dissertation also reports a study conducted to investigate the impact of tick bites on host sensitization and the induction of AGS in mice. This study found that mice sensitized with Am. americanum ticks expressing α-gal antigens showed a significant increase in total IgE, IgG1, and α-gal IgG1 antibodies compared to mice sensitized with Am. maculatum ticks, which lack α-gal antigens. After the pork meat challenge, mice sensitized by Am. americanum ticks showed elevated levels of total IgE, α-gal IgE, total IgG1, and α-gal IgG1 antibodies as well as lower core body temperature than control mice and mice sensitized with Am. maculatum. These findings suggest that tick bites from Am. americanum may induce AGS or lead to sensitization against the α-gal antigen. In addition, the study supports the hypothesis that only certain tick species may increase the risk of developing α-gal-specific IgE and hypersensitivity reactions, paving the way for future research into the mechanistic role of tick and host-associated factors in AGS development.

ORCID ID

0000-0002-9602-2874

Available for download on Thursday, March 27, 2025

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