Elucidating the role of early granuloma formation in dissemination during fungal infections in vivo. . (360G-Wellcome-108387_Z_15_Z)

Currently, over one billion fungal infections occur each year worldwide of which over two million develop into life-threatening invasive mycoses. At the same time, our current anti-fungal therapies are ineffective, expensive and show substantial side effects. As a result, up to 95% of patients with invasive fungal infections die. Several major fungal pathogens are known to induce the formation of granuloma tissue (e.g. Aspergillus, Cryptococcus, Histoplasma etc.). However, the function of th ese granulomas during fungal infections has not been studied to date. I propose to initiate a new line of research investigating the role of early granuloma formation during fungal infections using an in vivo zebrafish model. In particular, I propose to utilise this model in order to determine whether granuloma formation during fungal infection is protective (in trapping fungi) or damaging (in allowing persistence) to the host. This approach will provide information on the spatio-temporal pa tterns of granuloma formation and immune activation and how these correlate with disease dissemination. The data will be applied to explain the striking individual variability in susceptibility to and outcome of fungal infections.