Document Type

Honors Thesis

Major

Zoology

Advisor(s)

Robert Wheeler, Clarissa Henry

Committee Members

Mimi Killinger, Melody Neely, Jared Talbot

Graduation Year

May 2020

Publication Date

Spring 5-2022

Abstract

Throughout the United States and Europe, Candida albicans remains the most clinically significant fungus. While fungi account for thousands of deaths annually, the most clinically significant bloodstream infection in ICU patients, causing as high as 50% mortality, is disseminated candidemia. This systemic infection occurs when the normally commensal and harmless fungi, Candida albicans, becomes pathogenic in immunocompromised individuals. Many factors of the immune system can be paralleled between humans and zebrafish, which can be a useful model host to understand the cellular immune responses to infection. One particular gene known as myeloid differentiation factor 88 (myd88) has been previously found to be an important recruiter of immune cells in the innate immune response to infection. Paradoxically, previous work on mucosal infection in the zebrafish swimbladder did not show impaired macrophage recruitment between myd88 mutant fish and wild type fish, as was expected. In this Honors Thesis study, we aimed to investigate if this disconnect was due to myd88 playing a different role in mucosal vs. the disseminated infection models. myd88 was shown to protect against hindbrain infection. Additionally, we found that the NF-κB pathway was activated during a hindbrain infection, and appears to act independently of myd88. This may provide insight into the selective role myd88 plays in immunity to C. albicans in a localized hindbrain infection.

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