Osorio Olivares, F.B.; (2010) Role of Syk-coupled C-type lectin receptors in T cell immunity to fungal stimuli. Doctoral thesis , UCL (University College London).

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Abstract

Innate signals are fundamental to determine the class of adaptive response against infection. The translation of microbial signatures into adaptive immunity is mediated by pattern recognition receptors (PRRs), which are expressed in specialized leukocytes called dendritic cells (DCs) and results in responses matched to the nature of the offending microbe. Here, I provide evidence that two Syk-coupled C-type lectin receptors (CLRs), Dectin-1 and Dectin-2, act in the coordination of adaptive immune responses to fungal stimuli and fungal pathogens. DC activated via Dectin-1 are strong elicitors of IL-17 production by CD4+ T cells. Results presented in this thesis demonstrate that Dectin-1 signalling in DCs results in the generation and Foxp3+-IL-17+ T cells, a cell type that defies either regulatory or Th17 classification. This process is dependent on IL-23, which is produced by DCs upon Dectin-1 ligation. In addition, this work identified an additional CLR responsible for the induction of Th17 responses during the course of fungal infections. This thesis demonstrates that Dectin-2 is a second Syk-coupled PRR involved in DC activation by fungi. In a model of Candida albicans systemic infection, Dectin-2 is essential for the induction of Th17 responses to the organism. Finally, I have generated tools to study responses of T cells specific for a fungal-associated antigen. Furthermore, I provide preliminary evidence regarding the activation, proliferation and trafficking of antigen-specific CD4+ and CD8+ T cells during systemic fungal infections.

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