Comparative analysis of IRF and IFN-alpha expression in human plasmacytoid and monocyte-derived dendritic cells

produce high levels of type I IFN upon stimulation with viruses, while monocytes and monocyte-de-rived dendritic cells (MDDC) produce significantly lower levels. To find what determines the high pro-duction of type I IFN in PDC, we examined the relative levels of IRF transcription factors, some of which play critical roles in the induction of IFN. Furthermore, to determine whether the differ-ences could result from expression of distinct IFNA subtypes, the profile of IFNA genes expressed was examined. PDC responded equally well to stimula-tion with HSV-1 and Sendai virus (SV) by produc-ing high levels of type I IFN, whereas the MDDC and monocyte response to SV were much lower, and neither responded well to HSV-1. All three populations constitutively expressed most of the IRF genes. However, real-time RT-PCR demon-strated increased levels of IRF-7 transcripts in PDC compared with monocytes. As determined by intracellular flow cytometry, the PDC constitu-tively expressed significantly higher levels of IRF-7 protein than the other populations while IRF-3 levels were similar among populations. Analysis of the profile of IFNA genes expressed in virus-stim-ulated PDC, monocytes and MDDC demonstrated that each population expressed IFNA1 as the major subtype but that the range of the subtypes ex-pressed in PDC was broader, with some donor and stimulus-dependent variability. We conclude that PDC but not MDDC are uniquely preprogrammed to respond rapidly and effectively to a range of viral pathogens with high levels of IFN- produc-tion due to the high levels of constitutively ex