Genomic Survey of Cryptococcus neoformans-Induced Gene Expression Profiling in Human Brain Micro-Vascular Endothelial Cells

Cryptococcus neoformans is able to infect brain microvascular endothelial cells (BMEC). We performed microarray analysis of the changes in gene expression of human BMEC (HBMEC) to dissect the pathogenesis of this infection. Changes in mRNA levels were monitored at 0, 4, 8, 12, 16, 20 and 24 hours. Principal component analysis (PCA) revealed a fluctuation of gene groups during the pathogen-host interaction. Based on the time-course analysis, there are 91 and 89 genes that persistently increase and decrease their mRNA levels, respectively. The significant changes are immune responses to C. neoformans infection. Hierarchical cluster profile showed that 61 out of 66 listed interferon genes were changed at least at one time point. The active responses in expression ofMHC genes were also detected at all stages of the interaction. Taken together, our infectomic studies with linear PCA approach suggest that HBMEC significantly changes its gene profiling and also actively participates in immuno-regulations in the central nervous system during C. neoformans infection.