Coculture of THP‐1 Human Mononuclear Cells with Candida albicans Results in Pronounced Changes in Host Gene Expression
Departments of 1Pharmacy and 2Pharmaceutical Sciences, College of Pharmacy, and 3Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, and 4Children’s Foundation Research Center, Le Bonheur Children’s Medical Center, Memphis, Tennessee
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.
Received 10 February 2005; accepted 30 March 2005; electronically published 20 July 2005.
Cited by
Online publication date: 15-Jul-2008.
Online publication date: 1-Jul-2007.
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Online publication date: 15-Mar-2006.
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Presented in part: 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 27–30 September 2002 (poster M‐207).
Potential conflicts of interest: none reported.
Financial support: Center of Genomics and Bioinformatics, University of Tennessee Health Science Center.





