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, 192 (5), 901-12

Coculture of THP-1 Human Mononuclear Cells With Candida Albicans Results in Pronounced Changes in Host Gene Expression

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Coculture of THP-1 Human Mononuclear Cells With Candida Albicans Results in Pronounced Changes in Host Gene Expression

Katherine S Barker et al. J Infect Dis.

Abstract

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.

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