Semester

Summer

Date of Graduation

2022

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Microbiology, Immunology, and Cell Biology

Committee Chair

Christopher Cuff

Committee Co-Chair

Tara Croston

Committee Member

Mariette Barbier

Committee Member

Karen Dannemiller

Committee Member

Edwin Wan

Abstract

Allergic airway diseases such as asthma continue to increase in incidence in industrialized nations like the United States. These diseases are complex inflammatory processes involving numerous cells and mediators and are strongly influenced by fungal exposures. Recent developments in fungal detection methods have highlighted the contribution of Basidiomycota yeast species in indoor environments such as Vishniacozyma (syn. Cryptococcus) victoriae. However, despite the high levels of this yeast detected in indoor environments, very little is known about it or its role in respiratory morbidity. V. victoriae is phylogenetically similar to pathogenic Cryptococcus neoformans but lacks a capsule and is not known to be pathogenic. Epidemiological-based studies suggested varied impacts of Cryptococcus yeast species and allergic airway disease. For these reasons, this dissertation addresses the knowledge gap regarding the pulmonary inflammatory response to V. victoriae. First, V. victoriae was quantified in indoor environmental samples, and associations between this yeast and housing, environmental, and health data were examined. Then, the pulmonary immune response to repeated exposures to either V. victoriae or C. neoformans in mice was analyzed and compared. Lastly, the impact of repeated exposures to each yeast was examined in the context of an allergic airway disease model and proteomic analyses were conducted to start to identify potential mechanisms impacted because of V. victoriae exposure. Together, these findings show that exposure to Cryptococcus yeast species induces significant pulmonary inflammation and that the persistence of V. victoriae and C. neoformans following repeated exposure elicits unique pulmonary inflammatory responses. These results establish a crucial need for further exploration into yeast exposures, specifically Basidiomycota yeasts, and lay the groundwork for future investigations and policy decisions regarding exposure to yeast.

Embargo Reason

Publication Pending

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