title: Human monocytes represent a competitive source of interferon-alpha in peripheral blood.
abstract: Interferon-alpha (IFN-alpha) has a critical role in antiviral immunity and plasmacytoid dendritic cells (pDCs) have been demonstrated as the principal IFN-alpha source after Toll-like receptor (TLR) 7 and 9 stimulation. Little is known about the contribution of pDC-independent IFN-alpha sources to total IFN-alpha production capacity of human peripheral blood. Using an array of pathogen associated molecular patterns (PAMPs), Poly(I:C)/Dotap represented the second strongest IFN-alpha stimulus in total PBMC. Poly(I:C)/Dotap induced three times more IFN-alpha, when compared to TLR7-stimulation (R848) and four times less, when compared to TLR9-stimulation. Dotap (mediator of cellular uptake) dramatically increased Poly(I:C)-induced IFN-alpha production. Sorting experiments and ELISpot assays revealed that monocytes and not myeloid DCs are the main IFN-alpha source after Poly(I:C)/Dotap stimulation. ELISpot analyses demonstrated the highest IFN-alpha spot numbers after Poly(I:C)/Dotap stimulation. Although pDCs produced highest IFN-alpha levels per cell, monocytes represent a competing IFN-alpha source in total PBMC due to their high frequency.
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University Giessen, 35385 Giessen, Germany.
authors.forename: Leo
authors.initials: L
authors.lastname: Hansmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Groeger
authors.forename: Werner
authors.initials: W
authors.lastname: von Wulffen
authors.forename: Gregor
authors.initials: G
authors.lastname: Bein
authors.forename: Holger
authors.initials: H
authors.lastname: Hackstein
mesh_terms: D000328:Adult; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000276:immunology; D016130:Immunophenotyping / Q000379:methods; D016898:Interferon-alpha / Q000096:biosynthesis / Q000097:blood* / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D018709:Statistics, Nonparametric; D051199:Toll-Like Receptor 7 / Q000276:immunology
chemical_list: C513533:CpG ODN 2006; D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D007093:Imidazoles; D016898:Interferon-alpha; D018950:Lipopolysaccharide Receptors; D009838:Oligodeoxyribonucleotides; D000644:Quaternary Ammonium Compounds; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane; D011070:Poly I-C; C402365:resiquimod