کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5822194 1557834 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Analysis of the transcriptome and immune function of monocytes during IFNα-based therapy in chronic HCV revealed induction of TLR7 responsiveness
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
Analysis of the transcriptome and immune function of monocytes during IFNα-based therapy in chronic HCV revealed induction of TLR7 responsiveness
چکیده انگلیسی


- We examine the function and transcriptome of monocytes during IFNα-based therapy in HCV.
- IFNα-based therapy altered gene expression profiles, numbers and function of monocytes.
- IFNα-based therapy activated TLR7 signaling pathways in monocytes.
- IFNα-based therapy enhanced TLR7 responsiveness of monocytes.
- These findings are important since evaluation of TLR7 agonists as therapeutics in HCV.

Although in vitro studies have been performed to dissect the mechanism of action of IFNα, detailed in vivo studies on the long-term effects of IFNα on monocytes have not been performed. Here we examined peripheral blood from 14 chronic HCV patients at baseline and 12 weeks after start of IFNα-based therapy. Monocytes were phenotyped by flow-cytometry and their function evaluated upon TLR stimulation and assessed by multiplex cytokine assays.During therapy of HCV patients, monocytes displayed a hyperactive state as evidenced by increased TLR-induced pro-inflammatory cytokine levels, as well as enhanced CD69 and CD83 mRNA and protein expression. Moreover, monocytes from 8 patients at baseline and 12 weeks after start of IFNα-based therapy were transcriptomically profiled by high throughput RNA-sequencing. Detailed RNA-seq analysis of monocytes showed significant ISG mRNA induction during therapy. Importantly, IFNα-based therapy activated TLR7 signaling pathways, as demonstrated by up-regulated expression of TLR7, MyD88, and IRF7 mRNA, whereas other TLR family members as well as CD1c, CLEC4C, and CLEC9A were not induced. The induction of TLR7 responsiveness of monocytes by IFNα in vivo in HCV patients is relevant for the development of TLR7 agonists that are currently under development as a promising immunotherapeutic compounds to treat chronic viral hepatitis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 109, September 2014, Pages 116-124
نویسندگان
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