Master of Science in Biomedical Sciences (MSBS), University of Toledo, 2018, Biomedical Sciences (Bioinformatics and Proteomics/Genomics)

Oropharyngeal candidiasis (OPC) is a fungal infection of the oral cavity caused by a human commensal fungus called Candida albicans. Even though C. albicans is a commensal, it can become pathogenic in immunocompromised patients. IL-17-mediated antifungal immunity has been implicated as the major pathway for fungal defense in the oral cavity. The IL-17 pathway has been found to regulate the release of antimicrobial peptides (AMPs) downstream, including murine ß-defensin 3 (mBD3). Murine ß-defensin 3 is an antimicrobial peptide involved in the protection of the oral mucosa against pathogens. Murine BD3 can protect the oral mucosa through its direct antimicrobial activity, but it has also been found to have chemotactic properties as well. The human homolog of mBD3, human ß-defensin 2 (hBD2), has been found to bind CCR6. CCR6 is found on the surface of cells like memory T-cells, dendritic cells (DCs), Th17 cells, and Treg cells. Studies have shown that hBD2 binding to CCR6 on the surface of memory T-cells and DC's can induce chemotaxis, and other studies have suggested the same could be true for Th17 cells and Treg cells. The goal of this experiment was to study the chemotactic ability of mBD3 via RNA-sequencing to explore how the presence/absence of Defb3 leads to changes in transcriptional regulation while in the presence/absence of an OPC infection. The RNA-sequencing results reveal that there are very few differences in transcript expression between wild-type mice and Defb3 knockout mice. One difference in transcript expression between Defb3 knockout mice and WT mice is found in Sycp1. Sycp1 is expressed at higher levels in Defb3 knockout infected mice when compared with WT infected mice and Defb3 knockout sham mice when compared to WT sham mice. The DNA-binding ability of Sycp1 makes it an interesting candidate for future studies.

Committee: Heather Conti (Committee Chair); Sadik Khuder (Committee Member); Alexei Fedorov (Committee Member) Subjects: Bioinformatics; Biology; Immunology