Cryptococcus Neoformans Infection and Immune Cell Regulation in Human Monocytes.

BACKGROUND/AIMS: Cryptococcus neoformans infections are becoming increasingly prevalent and remain a life-threatening clinical issue in immune-compromised hosts. The microorganism evades a variety of endogenous anti-fungal mechanims of host immune cells. The signaling pathways in human immune cells that become activated in response to Cryptococcus neoformans infection have yet to be fully characterized.

METHODS

Human monocytes were incubated with Cryptococcus neoformans, and the whole transcriptome of monocytes was sequenced before and after exposure to Cryptococcus neoformans using mass parallel sequencing techniques. Based on the genes that demonstrated altered expression patterns, we performed GO and KEGG enrichment analysis to further characterize the pathways involved in monocyte activation by Cryptococcus neoformans.

RESULTS

We found that immune and inflammatory responses, as well as chemotaxis, were the most heavily activated cellular events. Specifically, the toll-like receptor, tumor necrosis factor, NF-kB and Jak-STAT pathways were the most active pathways in response to Cryptococcus neoformans infection. The sequencing data of selected genes from the transcriptome analysis were further validated by real-time polymerase chain reactions.

CONCLUSION

Taken together, our study is the first characterization of the transcriptome alterations in human immune cells upon C. neoformans infection, providing additional information that may be helpful in discovering novel anti-fungal targets.