Host-Microbe Interactions Between Cryptococcus neoformans and Phagocytes

The result of infection by the pathogenic fungus Cryptococcus neoformans is highly dependent on the outcome of interactions between yeasts and the cells of the host immune system. As such, investigations into the ability of C. neoformans to counter, evade, and co-opt mammalian immune systems are crucial to the understanding of cryptococcal pathogenesis and to the future development of methods by which infections can be treated. Furthermore, research into the environmental origins of C. neoformans virulence in mammals may provide insight into the origins of pathogenicity of multiple environmental or zoonotic diseases. Though much progress toward answering these questions has been made in the past half century, many important questions remain unanswered. This thesis contains just a few of the many attempts to chisel away at these big questions in the field. In Chapter 1, interactions between C. neoformans and murine macrophages are probed to determine how yeasts may manipulate the structure of the macrophage cytoskeleton during infection and how the immunological skew of macrophages affects this process. Chapter 2 contains efforts to use existing laboratory reagents to extend studies of the mammalian cell cytoskeleton to the actin structures of the soilborne and waterborne protozoan Acanthamoeba castellanii. Finally, in Chapter 3, the capacity for fungal adaptions to defeat mammalian immune systems was tested against environmental predator A. castellanii. While much remains to be done, these investigations may serve as a foundation upon which future experiments can be based and further exploration of host-pathogen interactions can be performed