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Title: The role of effector and regulatory helper T cells in a murine model of systemic Candida albicans infection
Author: Whibley, Natasha
ISNI:       0000 0004 2737 6657
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2013
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Diseases caused by fungi are increasing worldwide and are often associated with high mortality rates. In particular, the normally harmless commensal Candida albicans can cause serious disease if immunological and physiological barriers are perturbed, leading to systemic infection, which is fatal in up to 45% of cases. The adaptive immune response is believed to be important in protection against systemic candidiasis, however, the roles of different helper T (Th) cell subsets, particularly Foxp3+ regulatory T (Treg) cells, remain largely unexplored. The aims of this study were to adapt a mouse model of systemic C. albicans infection to test whether the numbers of Th1, Th2, Th17 and Foxp3+ Treg cells increase in mice with systemic C. albicans infection, and determine their contribution to disease. C. albicans drove the expansion of Th1, Th2 and Th17 cells, as well as multiple Foxp3+ populations that displayed characteristics of natural Treg, induced Treg, Th17 and Th1 cells in vitro and in vivo. The expanded Foxp3+ T cells inhibited Th1 and Th2, but promoted Th17, responses to C. albicans antigens in vitro and exacerbated disease, since their depletion in vivo reduced kidney fungal burden and inflammatory lesions. Furthermore, systemic infection with a weakly virulent C. albicans strain was associated with reduced Treg responses compared to those induced during lethal systemic infection. These data lead to a model for systemic candidiasis whereby Treg expansion promotes Th17 responses that drive pathology, and have implications for future immunotherapy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Candida albicans ; T-cells