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

• Type of Material: Article
• Authors: Yuwei Zhang, Hôpital Saint-Luc; Mohamed El-Far, Hôpital Saint-Luc; Franck P. Dupuy, Hôpital Saint-Luc; Mohamed Abdel Hakeem, Emory University; Zhong He, Hôpital Saint-Luc; Francesco Andrea Procopio, Hôpital Saint-Luc; Yu Shi, Hôpital Saint-Luc; Elias K. Haddad, Hôpital Saint-Luc; Petronela Ancuta, Hôpital Saint-Luc; Rafick-Pierre Sekaly, Emory University; Elias A. Said, Hôpital Saint-Luc
• Language: English
• Date: 2016-07-07
• Publisher: NATURE PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © 2016, Macmillan Publishers Limited
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/srep29447
• Title of Journal or Parent Work: SCIENTIFIC REPORTS
• Volume: 6
• Issue: 1
• Start Page: 29447
• End Page: 29447
• Keywords: TUMOR-NECROSIS-FACTOR; INFECTION; INNATE IMMUNITY; Multidisciplinary Sciences; HEPATITIS-C VIRUS; IFN; STAT1 ACTIVATION; DC-SIGN; Science & Technology - Other Topics; INTERFERON THERAPY; CPG DNA; Science & Technology; PLASMACYTOID DENDRITIC CELLS
• Research Categories: Biology, Virology; Health Sciences, Immunology; Biology, Genetics

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.