Identifying the mechanism of intracellular parasitism by Cryptococcus

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Cryptococcus is a free-living fungus that is able to cause a fatal infection in humans and other animals. Our current understanding of this disease suggests that fungal spores are inhaled into the lung and then ?hide? from the immune system, sometimes for several years, by living inside a particular type of host cell called a macrophage. Although this cell would kill most other pathogens, Cryptococcus has a remarkable ability to survive and indeed grow inside macrophages. In addition, we have recently discovered that the fungus is also able to ?escape? from inside of this host cell by a novel process called ?reverse phagocytosis?. This process is likely to be advantageous to the pathogen since it does not damage the host cell and is therefore unlikely to trigger a strong inflammatory response. In order to develop better treatments for this lethal disease, we need to understand how the fungus can manipulate the host cell in this way. Our application is therefore directed at learning more about the molecular process that underlies this behaviour. In particular, we hope to answer two specific questions:1) can we identify new ways in which human macrophages can be induced to destroy intracellular cryptococci and thereby eradicate latent infections?2) how great is the risk that particular strains of Cryptococcus will become more dangerous to patients by evolving an improved ability to manipulate host cells in this way?