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The Role of Antimicrobial Peptide Murine Beta Defensin-3 in Protection against Oropharyngeal Candidiasis

Mengesha, Bemnet Gashawbeza
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1510521465214606

Abstract Details

2017, Master of Science, University of Toledo, Biology (Cell-Molecular Biology).
Oropharyngeal candidiasis (OPC, thrush) is an opportunistic infection caused mainly by Candida albicans. C. albicans is a commensal of oral mucosal surfaces, but can be pathogenic when antifungal immune defense mechanisms are impaired. There is a high prevalence of OPC in patients with human immunodeficiency virus (HIV), implicating CD4+ T helper (Th) cells in protection against OPC. IL-17 is an important pro-inflammatory cytokine produced by the Th17 subset, and studies in experimental models show increased susceptibility in mice with impaired IL-17 signaling. Deficiencies in IL-17 signaling lead to defects including the production of antimicrobial peptides such as ß-Defensins (BDs). In OPC susceptible IL-17RA knockout mice, expression level of murine ß-defensins-3 (mBD3) is decreased in infected tongue tissue compared to wild type mice suggesting the involvement of mBD3 in protection against OPC. mBD3 has direct antifungal properties against Candida, but can also modulate the immune response through potential interactions with chemokine receptors such as CCR6 necessary for immune cell trafficking and recruitment. Moreover, mDefb3-/- mutant mice expressing low level of murine ß-Defensin-3 show high susceptibility to OPC suggesting the involvement of mBD3 in protection against OPC. Gene expression profile of mDefb3 -/- mice show impaired expression of IL-17 inducing cytokines such as IL1- ß and IL-6 and inflammatory cytokine IL-17 following Candida infection showing mDefb3 -/- mutant mice have defects in IL-17 signaling pathway. In addition, mDefb3 regulates expression of beta defensins mDefb1 (BD1), mDefb2 (BD2), chemokine CXCl2 but not chemokine CXCL1. Loss of expression of Defb3 in mDefb3 -/- mice was compensated by high expression of Defb14, and increased expression level of CCL20 early during infection (day 2 post infection) but was not enough to offset susceptibility to OPC. Using mouse model of OPC, we show that mDefb3 regulate innate immune response against OPC via regulation of AMPs (mDefb1 and mDefb2) and proinflammatory cytokines (IL-17, IL-6 and IL1ß).
Heather Conti (Committee Chair)
Malathi Krishnamurthy (Committee Member)
Jianyang Du (Committee Member)
69 p.
Biology; Biomedical Research
Oropharyngeal candidiasis; Candida albicans; murine beta defensin 3

Recommended Citations

Citations

  • Mengesha, B. G. (2017). The Role of Antimicrobial Peptide Murine Beta Defensin-3 in Protection against Oropharyngeal Candidiasis [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1510521465214606

    APA Style (7th edition)

  • Mengesha, Bemnet. The Role of Antimicrobial Peptide Murine Beta Defensin-3 in Protection against Oropharyngeal Candidiasis. 2017. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1510521465214606.

    MLA Style (8th edition)

  • Mengesha, Bemnet. "The Role of Antimicrobial Peptide Murine Beta Defensin-3 in Protection against Oropharyngeal Candidiasis." Master's thesis, University of Toledo, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1510521465214606

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Toledo and OhioLINK.