Date of Award

5-2022

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Committee Chair/Advisor

Emily Rosowski

Committee Member

Sourabh Dhingra

Committee Member

Yanzhang Wei

Abstract

Aspergillus fumigatus is a fungus found ubiquitously in the environment including in the air we breathe. Though not a threat to most people, immunodeficient or immunosuppressed individuals are at risk for developing severe infection, including the life-threatening condition of invasive aspergillosis. The hematopoietic cell specific GTPase protein Rac2 is associated with major roles in innate immune defense. Currently Rac2 has been demonstrated to be crucial for survival against a variety of infections. Here, we use a rac2 null mutant zebrafish line and morpholino approaches to elucidate roles of Rac2 in mounting the macrophage host defense response against A. fumigatus infection. Zebrafish provide an optimal model for studying host-pathogen interactions due to high compatibility with in vivo imaging techniques. Data demonstrates significantly impaired survival in zebrafish lacking Rac2 expression during A. fumigatus infection. In this infection, I have found that absence of Rac2 results in no impairment to macrophage migration or phagocytosis. Despite this apparent lack in major involvement of Rac2 in early macrophage response, I demonstrate that rac2 null mutants are characterized by significant impairment in ability to suppress germination, highlighting an important role for Rac2 in promoting the germination inhibiting activity of macrophages.

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