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Comparative analysis of IRF and IFN‐alpha expression in human plasmacytoid and monocyte‐derived dendritic cells
Author(s) -
Izaguirre Alexander,
Barnes Betsy J.,
Amrute Sheela,
Yeow WenShuz,
Megjugorac Nicholas,
Dai Jihong,
Feng Di,
Chung Eugene,
Pitha Paula M.,
FitzgeraldBocarsly Patricia
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0603255
Subject(s) - biology , sendai virus , flow cytometry , monocyte , interferon , plasmacytoid dendritic cell , dendritic cell , population , immunology , alpha interferon , interferon type i , stimulation , microbiology and biotechnology , virus , virology , immune system , endocrinology , demography , sociology
Plasmacytoid dendritic cells (PDC) produce high levels of type I IFN upon stimulation with viruses, while monocytes and monocyte‐derived dendritic cells (MDDC) produce significantly lower levels. To find what determines the high production 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 differences could result from expression of distinct IFNA subtypes, the profile of IFNA genes expressed was examined. PDC responded equally well to stimulation with HSV‐1 and Sendai virus (SV) by producing high levels of type I IFN, whereas the MDDC and monocyte response to SV were lower, and neither responded well to HSV‐1. All three populations constitutively expressed most of the IRF genes. However, real‐time RT‐PCR demonstrated increased levels of IRF‐7 transcripts in PDC compared with monocytes. As determined by intracellular flow cytometry, the PDC constitutively 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‐stimulated PDC, monocytes and MDDC demonstrated that each population expressed IFNA1 as the major subtype but that the range of the subtypes expressed 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‐α production due to the high levels of constitutively expressed IRF‐7.