Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799521
Title: High-resolution automated analysis of early phases of Aspergillus fumigatus infection of lung epithelial cells
Author: Ben Ghazzi, Nagwa
ISNI:       0000 0004 8505 1914
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2020
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Abstract:
Survival of A. fumigatus within lung epithelial cells is related to several complicated developmental dynamics and behavioural strategies. Additionally, proper and effective host immunological responses to control fungal survival, growth, and invasion can prevent in dissemination to other organs. Since phagosome maturation is vital for successful phagocytosis, many pathogens have developed diverse strategies to interfere with phagosome maturation, to avoid killing and survive within the cell or to escape extracellularly. Little quantitative data is available concerning the dynamics of A. fumigatus cell biology as well as strategies adopted by the fungus within lung epithelial cells for survival and growth. Also, it remains unclear whether phagosome maturation is manipulated by the internalized A. fumigatus spore. It is also unknown whether A. fumigatus spore killing requires phagosome maturation. An automated system was developed to quantify active cell biology events during phagocytosis of A. fumigatus by lung epithelial cells. My work has clearly shown that both bronchial and alveolar epithelial cells ingest and kill A. fumigates spores as well as hyphae, with ~2% persisting for more than 48 hours. Also, the survival and growth of A. fumigatus spore within lung epithelium is correlated with suboptimal or partial phagosome maturation. Moreover, it was observed that germinated spore can escape the epithelial cells causing cell death. Bronchial cells are more effective in killing spores than alveolar cells. Several fungal factors affecting this process include dopP and ptyA. Deletion of the sreA gene demonstrated that iron acquisition is essential in phagosome effectiveness. To conclude, an automated system was developed to quantify cell biology dynamics during phagocytosis of A. fumigatus by lung epithelial cells. Evidently, it was demonstrated that both bronchial and alveolar cells ingest and kill A. fumigates spores as well as hyphae, in which bronchial cells are more effective, although some spores could persist more than 48 hours, allowing growth and epithelial cell death. Fungal dopP and ptyA have a role in interfering with phagosome maturation. Also, lack of the sreA gene demonstrated that iron ions are essential in phagosome effectiveness against A. fumigatus.
Supervisor: Denning, David ; Bromley, Michael ; Bowyer, Paul Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.799521  DOI: Not available
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