Interferon-Beta Induces Distinct Gene Expression Response Patterns in Human Monocytes versus T cells

Background: Monocytes, which are key players in innate immunity, are outnumbered by neutrophils and lymphocytes among peripheral white blood cells. The cytokine interferon-beta (IFN-beta) is widely used as an immunomodulatory drug for multiple sclerosis and its functional pathways in peripheral blood mononuclear cells (PBMCs) have been previously described. The aim of the present study was to identify novel, cell-specific IFN-beta functions and pathways in tumor necrosis factor (TNF)-alpha-activated monocytes that may have been missed in studies using PBMCs. Methodology/Principal Findings: Whole genome gene expression profiles of human monocytes and T cells were compared following in vitro priming to TNF-alpha and overnight exposure to IFN-beta. Statistical analyses of the gene expression data revealed a cell-type-specific change of 699 transcripts, 667 monocyte-specific transcripts, 21 T cell-specific transcripts and 11 transcripts with either a difference in the response direction or a difference in the magnitude of response. RT-PCR revealed a set of differentially expressed genes (DEGs), exhibiting responses to IFN-beta that are modulated by TNF-alpha in monocytes, such as RIPK2 and CD83, but not in T cells or PBMCs. Known IFN-beta promoter response elements, such as ISRE, were enriched in T cell DEGs but not in monocyte DEGs. The overall directionality of the gene expression regulation by IFN-beta was different in T cells and monocytes, with up-regulation more prevalent in T cells, and a similar extent of up and down-regulation recorded in monocytes. Conclusions: By focusing on the response of distinct cell types and by evaluating the combined effects of two cytokines with pro and anti-inflammatory activities, we were able to present two new findings First, new IFN-beta response pathways and genes, some of which were monocytes specific; second, a cell-specific modulation of the IFN-beta response transcriptome by TNF-alpha.