کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3352123 1216458 2007 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibitory oligodeoxynucleotides downregulate herpes simplex virus-induced plasmacytoid dendritic cell type I interferon production and modulate cell function
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Inhibitory oligodeoxynucleotides downregulate herpes simplex virus-induced plasmacytoid dendritic cell type I interferon production and modulate cell function
چکیده انگلیسی

SummaryRecognition of nucleic acids by TLR9 expressed by human plasmacytoid dendritic cells (PDC) plays a key role in the defense against viral infections. Upon microbial pathogen stimulation, PDC secrete large amounts of type I interferon and arbitrate thereby both innate and adaptive immune mechanisms. Unmethylated CpG motifs, which are an integral part of bacterial or viral DNA, are used in vitro and in vivo to activate the TLR9 pathway, whereas inhibitory oligodeoxynucleotide (iODN) are capable of depressing TLR9 signaling. In this study we demonstrate that TTAGGG motifs containing iODN efficiently block the TLR9 signaling in terms of herpes simplex virus (HSV)-induced type I interferon production by PDC. However, iODN, as well as control ODN, still promote PDC maturation with upregulated expression of costimulatory molecules, major histocompatibility complex molecules, and other signs for PDC maturation. Furthermore, iODN and control ODN incubated PDC demonstrate increased T-cell stimulatory functions. Coculture experiments with autologous T cells indicate that iODN-treated PDC induce more CD4+CD25+Foxp3+ T regulatory cells from naive CD4+ T cells and preincubation of HSV-stimulated PDC with iODN upregulated T cells′ IFN-γ production. These data indicate that iODN, while blocking type I interferon production by PDC, modify PDC activation and maturation as well as T-cell priming and stimulation. Knowledge about the different functions of iODN on PDC elucidated might be crucial for immunotherapeutic strategies in which iODN motifs are used to prevent the interaction of CpG-DNA with TLR9 to calm down specific immunological responses, because our data indicate that iODN might not only have inhibitory functions but also be effective activators of immune cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Human Immunology - Volume 68, Issue 11, November 2007, Pages 879–887
نویسندگان
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