Cryptococcus Neoformans Infection and Immune Cell Regulation in Human Monocytes.
OBJECTIVE
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.


CONCLUSIONS
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.
Sunxiao
S
Chen
Hongli
H
Yan
Lei
L
Zhang
Wei
W
Kong
Yi
Y
Sun
Weiwei
W
Zhang
Yan
Y
Chen
Anmei
A
Deng
D003453:Cryptococcosis / Q000276:immunology / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000276:immunology / Q000472:pathogenicity*; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D063990:Gene Ontology; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D053612:Janus Kinases / Q000235:genetics; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology*; D016328:NF-kappa B / Q000235:genetics; D050791:STAT Transcription Factors / Q000235:genetics; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016328:NF-kappa B; D050791:STAT Transcription Factors; C439524:TNF protein, human; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D053612:Janus Kinases