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HCV RNA Activates APCs via TLR7/TLR8 While Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses.

Abstract：

:The innate and adaptive immune systems fail to control HCV infection in the majority of infected individuals. HCV is an ssRNA virus, which suggests a role for Toll-like receptors (TLRs) 7 and 8 in initiating the anti-viral response. Here we demonstrate that HCV genomic RNA harbours specific sequences that initiate an anti-HCV immune response through TLR7 and TLR8 in various antigen presenting cells. Conversely, HCV particles are detected by macrophages, but not by monocytes and DCs, through a TLR7/8 dependent mechanism; this leads to chloroquine sensitive production of pro-inflammatory cytokines including IL-1β, while the antiviral type I Interferon response is not triggered in these cells. Antibodies to DC-SIGN, a c-type lectin selectively expressed by macrophages but not pDCs or mDCs, block the production of cytokines. Novel anti-HCV vaccination strategies should target the induction of TLR7/8 stimulation in APCs in order to establish potent immune responses against HCV.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Zhang Y,El-Far M,Dupuy FP,Abdel-Hakeem MS,He Z,Procopio FA,Shi Y,Haddad EK,Ancuta P,Sekaly RP,Said EA

doi

10.1038/srep29447

subject

Has Abstract

pub_date

2016-07-07 00:00:00

pages

29447

issn

2045-2322

pii

srep29447

journal_volume

6

pub_type

杂志文章

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