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Title: Characterisation of the differential phagocytic, cytokine and T cell activation potentials of bone marrow derived dendritic cells in response to C.albincans cell wall glycosylation
Author: Gibson, Joanne
ISNI:       0000 0004 2707 3314
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2011
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This thesis study investigated the involvement of glycosylation of cell wall proteins, major components of the outermost cell wall layer of C. albicans, in the induction of murine bone marrow derived dendritic cell (BMDC) responses. Utilising mutants which are deficient in glycosylation process, the binding of specific N-glycosylation moieties was demonstrated to be important in triggering phagocytosis while changes in O-glycosylation moieties altered the secretion of multiple pro-inflammatory chemokines and cytokines. Importantly, BMDC-O-glycosylation and/or BMDC-inner cell wall constituent interactions were demonstrated to result in the modulation of T cell responses, through the stimulation of the secretion of interleukin (IL)-17. It was further shown using receptor-deficient BMDC and receptor-blocking antibodies that although dectin-1, mannose receptor (MR) and Toll-like receptor (TLR)4 do not play a role in the induction of phagocytosis, receptor engagement induced receptor-specific cytokine secretion. Specifically, the secretion of IL-12p70 and IL-6 was dependent on dectin-1 signalling, while the secretion of the pro-inflammatory monocyte chemotactic protein (MCP)-1, tumour necrosis factor (TNF)-α and IL-6 were found to be induced in a MR-dependent manner. Intriguingly, a redundant role was found for TLR4. Cumulatively these results indicate a critical role of the recognition of fungal cell wall glycosylation moieties in the induction of protective phagocytosis and cytokine response in BMDC. Future studies to determine the role of other lectin receptors such as dectin-2 or receptor combinations will provide further insights into the complex interactions between BMDC and C. albicans.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available