Date of Award

2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Abstract

Aspergillus fumigatus is a ubiquitous airborne fungus which is associated with the development of various pulmonary diseases, like fatal invasive aspergillosis (IA), particularly in immunocompromised patients. FIBrinogen C Domain containing 1 (FIBCD1) is a tetrameric receptor that binds chitin, is found in human lung epithelium, and modulates lung epithelial inflammatory responses to A. fumigatus cell wall polysaccharides. However, little is known about the role of FIBCD1 in the context of fungal infection, especially the murine pulmonary model of IA. Not much is known about the role of FIBCD1 in other fungal infection models like systemic fungal infection, where the infection is not limited to one particular organ. This study aims to determine the role of FIBCD1 in lung immune cell activation and recruitment, cytokine production, and fungal clearance in response to A.fumigatus infection and acute lung injury, using both in vitro and in vivo strategies. Here, I demonstrate that FIBCD1 has a detrimental role in the murine pulmonary model of IA and modulates inflammatory cell recruitment and cytokine expression. Moreover, FIBCD1-deficiency had no significant effect on morbidity and mortality of systemic fungal infection or in acute lung injury. FIBCD1 expression or deficiency modulated the overall immune responses to chitin in lungs, in in vitro and in vivo models. These results suggest a detrimental role for FIBCD1 anti-fungal immunity and introduces new possibilities for novel therapeutic targets.

Share

COinS