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Title: Anti-fungal immunity and the role of Dectin-1
Author: Vautier, Simon M. J.
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2013
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Candida albicans is a member of the human microbiota and normally maintains a commensal relationship with the host. However, C. albicans is an opportunistic pathogen and can cause both mucosal and life threatening systemic infections. Dectin-1 is a pattern recognition receptor and part of the innate immune system. Although Dectin-1 is essential in controlling a number of fungal infections its exact role during C. albicans infections is controversial due to two conflicting reports from the Iwakura and Brown groups. This thesis demonstrates that this controversy is due, at least in part, to strain specific adaptions to the host, resulting in the modulation of cell wall content and structure, in particular chitin levels. Having resolved this controversy the role of Dectin-1 in controlling C. albicans growth within the gastrointestinal tract following systemic and oral infection is determined. Following systemic infection Dectin-1 plays an essential role in the innate immune response controlling fungal growth, with Dectin-1 deficiency leading to increased fungal burdens and aberrant cytokine responses. Surprisingly, no requirement for Dectin-1 in the control of C. albicans colonization of the GI tract was demonstrated following oral infection. Thus in murine models Dectin-1 is essential for controlling systemic C. albicans infection, but appears to be redundant in controlling C. albicans colonisation of the GI tract following infection by the oral route. How C. albicans morphology affects colonisation of the GI tract and host immune responses are poorly understood. Here it is demonstrated that filamentous morphologies are less able to colonise the GI tract than yeast forms, with a yeast favouring environment existing within the GI tract. However, limitations of the models used here cloud the exact immune responses to C. albicans morphological forms but give valuable insights into the complexity of host pathogen interactions. The results presented here provide substantial new insights into C. albicans adaptions to the host and have important implications for understanding susceptibility to and treatment of C. albicans infections.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Candida albicans ; Antifungal agents