Coculture of THP-1 human mononuclear cells with Candida albicans results in pronounced changes in host gene expression.
BACKGROUND
The host's first line of defense against bloodstream infection with Candida albicans involves the recognition and clearance of the fungus by neutrophils and monocytes/macrophages. The purpose of the present study was to examine changes in the monocytic cell gene-expression profile in response to C. albicans stimulation.


METHODS
RNA was isolated from THP-1 cells 3 h after coculture with live C. albicans SC5314 cells. After hybridization to microarrays, genes differentially expressed by at least 2.0-fold were included in the final data set.


RESULTS
As expected, TNFA, IL8, CD83, MIP1A, and MIP1B were among the genes up-regulated. This was confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR), fluorescence-activated cell sorting analysis, and enzyme-linked immunosorbent assay. Furthermore, RGS1, RGS2, RGS16, DSCR1, GROB, EGR3, FLT4, and TNFAIP6 were also up-regulated in response to C. albicans, whereas CCR2 and NCF2 were among the genes down-regulated in response to C. albicans. Differential expression of selected genes was confirmed at several time points by real-time RT-PCR.


CONCLUSIONS
This study defines the gene expression profile of an early response of human mononuclear cells to C. albicans and identifies genes not previously known to be responsive to this pathogen.
Barker
Katherine S
KS
Department of Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA. ksbarker@utmem.edu
Liu
Teresa
T
Rogers
P David
PD
D002176:Candida albicans / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D012313:RNA