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CC BY-NC V4.0, Open Access
Dissertation
THE ROLE OF NEUROMEDIN U RECEPTOR 1 IN REGULATING DISTINCT INNATE IMMUNE RESPONSES TO DIFFERENT PATHOGENS IN C. ELEGANS
Washington State University
Doctor of Philosophy (PhD), Washington State University
01/2022
DOI:
https://doi.org/10.7273/000004375
Handle:
https://hdl.handle.net/2376/125199
Abstract
Two of the most complex systems found in mammals are the nervous system and the immune system. Both systems interpret cues from the environment and relay that information across the body, allowing the body as a whole to maintain homeostasis. How these two systems interact, and share information is a key point of interest, as understanding this communication pathway can help researchers develop more effective treatments to a growing list of autoimmune and infectious diseases. Using the soil dwelling nematode, Caenorhabditis elegans, we examined the role of NMUR-1, a neuronal G protein-coupled receptor homologous to mammalian receptors for the neuropeptide neuromedin U, in this communication pathway. We demonstrated that a lack of this neuronally expressed GPCR has distinct effects on C. elegans innate immune response, mutant animals survived longer against the pathogen Salmonella enterica but had a significantly shorter survival against Enterococcus faecalis. Utilizing both an in vitro and in vivo transcriptomic analyses along with functional assays revealed that NMUR-1 regulates the transcription factors associated with RNA polymerase II, which in turn, regulates a distinct immune response to the various pathogens. During E. faecalis infection, genes in the C-type lectin family are upregulated in wild-type animals but the same genes in a nmur-1 mutant background are significantly suppressed. S. enterica infection by contrast causes a suppression of unfold protein response related genes in wild-type animals and an upregulation of the same genes in nmur-1 mutants. Transgenically expressing these distinct immune response genes, increased survival of wild-type animals on S. enterica and nmur-1 mutant animals on E. faecalis. Further, proteomic analysis during infection showed that NMUR-1 regulates both the catalytic and motor subunits of F1F0 ATP synthase which also contributed to the pathogenesis of specific bacteria. Silencing the catalytic subunits of the F1F0 subunits using RNAi or preventing the mechanical rotation of the motor units increased the survial of wild-type animals against S. enterica while reducing their survival against E. faecalis. In this dissertation the molecular and cellular basis of the specificity of the innate immune responses against pathogen infections in C. elegans will be dissected.
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Details
- Title
- THE ROLE OF NEUROMEDIN U RECEPTOR 1 IN REGULATING DISTINCT INNATE IMMUNE RESPONSES TO DIFFERENT PATHOGENS IN C. ELEGANS
- Creators
- Phillip James Wibisono
- Contributors
- Jingru Sun (Advisor)K. Michael Gibson (Committee Member)Kathryn Meier (Committee Member)Jennifer Watts (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- College of Pharmacy and Pharmaceutical Sciences
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 191
- Identifiers
- 99900883134901842
- Language
- English
- Resource Type
- Dissertation