Characterisation of Aspergillus fumigatus Endocytic Trafficking within Airway Epithelial Cells Using High-Resolution Automated Quantitative Confocal Microscopy
AuthorsBen-Ghazzi, Nagwa; email: firstname.lastname@example.org
Moreno-Velásquez, Sergio; email: email@example.com
Seidel, Constanze; email: firstname.lastname@example.org
Thomson, Darren; orcid: 0000-0002-4800-7717; email: email@example.com
Denning, David W.; email: firstname.lastname@example.org
Read, Nick D.; email: email@example.com
Bowyer, Paul; email: firstname.lastname@example.org
Gago, Sara; orcid: 0000-0002-7027-4598; email: email@example.com
MetadataShow full item record
AbstractThe precise characterization of the mechanisms modulating Aspergillus fumigatus survival within airway epithelial cells has been impaired by the lack of live-cell imaging technologies and user-friendly quantification approaches. Here we described the use of an automated image analysis pipeline to estimate the proportion of A. fumigatus spores taken up by airway epithelial cells, those contained within phagolysosomes or acidified phagosomes, along with the fungal factors contributing to these processes. Coupling the use of fluorescent A. fumigatus strains and fluorescent epithelial probes targeting lysosomes, acidified compartments and cell membrane, we found that both the efficacy of lysosome recruitment to phagosomes and phagosome acidification determines the capacity of airway epithelial cells to contain A. fumigatus growth. Overall, the capability of the airway epithelium to prevent A. fumigatus survival was higher in bronchial epithelial than alveolar epithelial cells. Certain A. fumigatus cell wall mutants influenced phagosome maturation in airway epithelial cells. Taken together, this live-cell 4D imaging approach allows observation and measurement of the very early processes of A. fumigatus interaction within live airway epithelial monolayers.
CitationJournal of Fungi, volume 7, issue 6, page e454
DescriptionFrom MDPI via Jisc Publications Router
History: accepted 2021-06-02, pub-electronic 2021-06-07
Publication status: Published
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research; Grant(s): NC/P002390/1
Funder: German Science Fundation; Grant(s): DFG, SE2405/1-1
Funder: Libyan Ministry of Higher Education and Scientific Research; Grant(s): NA
Funder: Consejo Nacional de Ciencia y Tecnología; Grant(s): 359173
Funder: NIHR Manchester Biomedical Research Centre; Grant(s): NA
Funder: FP7 Ideas: European Research Council; Grant(s): PITN-GA-520 2013-607963
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