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Conditional immortalisation of myeloid-precursors to model innate immunity

McDonald, Jacqueline 2013. Conditional immortalisation of myeloid-precursors to model innate immunity. PhD Thesis, Cardiff University.
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Abstract

The prevalence of fungal infections is on the rise due to the increase of immune suppressed individuals. Neutrophils are key immune cells in the fight against fungal infections. The study of neutrophil biology is hampered by the short lived nature of the cells and the fact that they cannot be easily genetically modified. In this thesis, I generate and characterise myeloid precursor cell lines that can be genetically manipulated and differentiated into functional neutrophils. These in vitro generated neutrophils were adoptively transferred into live animals and tracked during inflammatory responses. Clec7a, a cell surface β-glucan receptor found on myeloid cells, and its role in immune response to fungal infections has been well characterised in macrophages and dendritic cells but less so on neutrophils. In this thesis, a model for elucidating the role of Clec7a on neutrophils was developed using primary cells and was able to show that Clec7a deficiency on neutrophils impairs recognition of zymosan and C. albicans but that this impairment was largely overcome by serum opsonisation of the particles. The in vitro generated neutrophils were comparably tested and, although the cells have their limitations, they largely supported the conclusions found using primary cells.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Medicine
Subjects: Q Science > QR Microbiology > QR180 Immunology
Date of First Compliant Deposit: 30 March 2016
Last Modified: 19 Mar 2016 23:17
URI: http://orca.cf.ac.uk/id/eprint/45729

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