Advancing the understanding and measurement of phagocyte vomocytosis of Cryptococcus neoformans

Following digestion by phagocytes, the fungal pathogen Cryptococcus neoformans (CN) has been observed to survive within the normally fatal phagosome and trigger nonlytic expulsion through a process called “vomocytosis”. This phenomenon is believed to play a key role in dissemination of the fungal pathogen, allowing CN to use immune cells as shuttles to travel throughout the body and to even cross the blood brain barrier through a “Trojan Horse” method. Very little is known about the underlying mechanisms of vomocytosis; however, prior studies have correlated its rate of occurrence with a limited number of physicochemical, protein, and immunological cues. Understanding vomocytosis could open the doors for the discovery of new therapies against Cryptococcal infection, as well as the development of novel drug delivery biomaterial vehicles with the ability to escape phagosome-mediated degradation. The primary goal of this thesis is to uncover further understanding of vomocytosis. This work contains (i) the discovery and characterization of this phenomenon’s occurrence in dendritic cells, a key player in bridging the innate and adaptive immune system, (ii) the development of a new fluorescent tool to measure vomocytosis rates in an objective, high throughput manner, and (iii) transcriptomic analysis of CN-infected phagocytes for identification of potential pathways and genes that regulate this process