Dissertation
Unraveling Arthropod Immunity: The unfolded protein response initiates the immune deficiency pathway in Ixodes scapularis ticks
Washington State University
Doctor of Philosophy (PhD), Washington State University
2023
DOI:
https://doi.org/10.7273/000006305
Abstract
Arthropod immunity impacts vector competency, which is the ability of a vector to acquire, maintain and transmit a pathogen. The well-studied insect model organism, Drosophila melanogaster, has been instrumental to the field of arthropod immunity. However, significant differences exist between insects and non-insect arthropods, such as ticks. One such distinction lies in the immune deficiency (IMD) pathway. In Drosophila, the pathway is activated by peptidoglycan recognition proteins (PGRPs) which then recruit adapter molecules IMD, FADD and DREDD, leading to downstream activation of the NF-kB factor, Relish. The initiating molecules, PGRPs, IMD, and FADD are not encoded in the genome of I. scapularis ticks but the core signaling components are conserved, and functionally limit bacterial colonization. What molecules or cellular processes initiating activation are not well-defined. Cellular stress responses, like the unfolded protein response (UPR), are increasingly being linked to innate immunity. In mammals, the TNFR pathway crosstalks with the UPR through the adaptor protein, TNF-receptor associated factor-2 (TRAF2). Whether the UPR influences immunity in arthropods has never previously been studied. Herein, we discovered the UPR receptor, IRE1α directly interacts with TRAF2 and limits colonization of Anaplasma phagocytophilum (Anaplasmosis) and Borrelia burgdorferi (Lyme disease) in ticks in vivo and in vitro. Moreover, this interaction leads to Relish activation, indicating a noncanonical mode of IMD pathway activation. The mechanistic linkage between IRE1α-TRAF2 and the IMD pathway remains undetermined.
Interrogating molecular interactions in ticks poses a challenge owing to the lack of genetic tools and resources available for non-model organisms. To address this limitation, we adapted an APEX2 proximity-based labeling assay for the use in Ixodes scapularis. This assay captures protein-protein interactions through biotinylation. By expressing recombinant TRAF2 fused to APEX2, we found Ixodes TRAF2 directly interacts with IKKγ, a component of the IKK complex, in which leads to IMD pathway activation. Overall, these finding provide valuable insight into the linkage between cellular stress responses and innate immunity in I. scapularis ticks. This research also enhances our understanding of arthropod immunity and vector competency, potentially paving the way for innovative strategies to control pathogen transmission.
Metrics
14 File views/ downloads
34 Record Views
Details
- Title
- Unraveling Arthropod Immunity
- Creators
- Lindsay Catherine Sidak-Loftis
- Contributors
- Dana K Shaw (Advisor)Alan Goodman (Committee Member)Troy Bankhead (Committee Member)Chrissy Eckstrand (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- College of Veterinary Medicine
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 148
- Identifiers
- 99901086721701842
- Language
- English
- Resource Type
- Dissertation