Cryptococcus neoformans is a neurotropic pathogen that causes fatal meningoencephalitis primarily in individuals with T-cell deficiency such as the AIDS patients. However, the fungus also causes infection in otherwise normal patients at a low frequency. The disease is 100% fatal unless treated and even with the most effective antimycotic agents, the fatality rate is about 25%. C. neoformans is commonly found in the human environment world-wide. In previous years, we discovered that C. neoformans yeast cells invaded the brain by crossing the blood-brain barrier transcellularly. We also, we reported that the CPS1 gene plays an important role in association and trversal of C. neoformans yeast cells across the blood-brain barrier (BBB). During the period of 2007-2008, we have characterized the CPS1 gene product as hyaluronic acid which is located at the base of the extracellular polysaccharide that surrounds the yeast cells. We also showed, in collaboration with Dr. Jong's group, that protein kinase C-alpha activation is required for the yeast to cross the BBB and CD44 is involved in the association of the yeast cells with the brain microvasular endothelial cells. While our research on the importance of the capsule for virulence of C. neoformans was going on, we analyzed the transcriptional profiles of dendritic cells that were exposed to encapsulated vs acapsular yeast cells. We showed that various proinflamatory cytokines are highly upregulated in dendritic cells exposed to acapsular cells while no such transcriptional changes were seen in dendritic cells exposed to encapsulated cells. These results corroborate previous immunological assays performed in macrophages that were exposed to encapsulated vs acapsular yeast.
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