C-type lectins in antifungal immunity (360G-Wellcome-217163_Z_19_Z)

I have established that C-type lectin receptors (CLRs) play a central role in antifungal immunity. In this proposal, I will capitalize on our exciting recent discoveries to address two questions that represent novel aspects of CLR biology: How do CLRs regulate antifungal adaptive immunity? We discovered dendritic cell expressed CLRs, the KLRs, which regulate the development of adaptive immunity during fungal infection. Our objective is to determine the physiological role of the KLRs, elucidating their cellular expression and function, the nature of their T-cell ligand(s), their influence on T-cell immunity and their importance in anti-fungal immunity. What is the impact of fungal secondary metabolite recognition by CLRs? We identified two novel CLRs that recognise fungal secondary metabolites, including secreted toxins such as aflatoxin (a major clinically significant fungal-derived carcinogen). Our objective is to gain a definitive understanding of the functions of these receptors and the immunological and physiological impact of their ability to recognise these secreted fungal products. Using a variety of in vivo and in vitro approaches, this research programme will significantly advance our knowledge of the underlying mechanisms of antifungal immunity, and will open new fields of investigation in the areas of adaptive immunity and medical mycology.