Cryptococcal infection occurs, in almost all cases, through the lungs. With a functional immune system this will cause little problem and will be cleared without clinical intervention. The mechanisms of clearance are incompletely understood but most likely require a granuloma-like response (for a review of the immune response to Cryptococcus see Gibson and Johnston, 2015). Susceptibility to uncontrolled cryptococcal infection is commonly associated with T-cell defects, most notably in HIV infection.
We are investigating if it is possible that macrophages might be activated to clear crytpococcal infection in the absence of a T-helper cell response. We are using zebrafish and in vitro cell models to understand the mechanisms of cryptococcal killing and the required signalling pathways. The long term aim of this project is to provide possible therapeutic paths for the functional macrophage defects seen in the immunocompromised.