My group are interested in host-pathogen interactions and, in particular, in understanding how some pathogens are able to subvert the innate immune system. Most of our work focuses on phagocytic cells, which some microorganisms are able to use as a ‘safe house’ within which to replicate. We try and understand how such pathogens can survive inside this hostile environment and the effect this intracellular reservoir has on disease progression.
The major focus of our group is on fungal infections, with a particular interest in cryptococcosis. This potentially fatal disease is caused by two pathogenic species of Cryptococci, Cryptococcus neoformans and C. gattii, which share a remarkable ability to evade the innate immune system and disseminate throughout the body. This is thought, in large part, to be the result of natural selection through environmental amoebae, since virulence traits that the fungus has evolved to survive within such predators typically work just as effectively within human phagocytes.
In this talk I will discuss our recent work in probing the cryptococcal/macrophage interaction. On the “host side”, I will discuss what we have learned about the molecular basis of “vomocytosis”: a poorly-understood process that phagocytes use to expel resistant pathogens which appears to be strongly modulated by inflammatory signals. From the “pathogen side” I will talk about our recent discovery of ‘long-range virulence control’ in Cryptococci, and what this might mean for our understanding of disease pathogenesis in patients.