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

Yuwei Zhang, Mohamed El-Far, Franck P. Dupuy, Mohamed S. Abdel-Hakeem, Zhong He, Francesco Andrea Procopio, Yu Shi, Elias K. Haddad, Petronela Ancuta, Rafick Pierre Sekaly, Elias A. Said

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Article number29447
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Jul 7 2016

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Antiviral Agents
Toll-Like Receptor 8
Toll-Like Receptor 7
Macrophages
RNA
Cytokines
Viruses
Interferon Type I
Chloroquine
Antigen-Presenting Cells
Infection Control
Interleukin-1
Lectins
Monocytes
Immune System
Vaccination
Antibodies
DC-specific ICAM-3 grabbing nonintegrin

ASJC Scopus subject areas

  • General

Cite this

HCV RNA Activates APCs via TLR7/TLR8 while Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses. / Zhang, Yuwei; El-Far, Mohamed; Dupuy, Franck P.; Abdel-Hakeem, Mohamed S.; He, Zhong; Procopio, Francesco Andrea; Shi, Yu; Haddad, Elias K.; Ancuta, Petronela; Sekaly, Rafick Pierre; Said, Elias A.

In: Scientific Reports, Vol. 6, 29447, 07.07.2016.

Research output: Contribution to journalArticle

Zhang, Y, El-Far, M, Dupuy, FP, Abdel-Hakeem, MS, He, Z, Procopio, FA, Shi, Y, Haddad, EK, Ancuta, P, Sekaly, RP & Said, EA 2016, 'HCV RNA Activates APCs via TLR7/TLR8 while Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses', Scientific Reports, vol. 6, 29447. https://doi.org/10.1038/srep29447
Zhang, Yuwei ; El-Far, Mohamed ; Dupuy, Franck P. ; Abdel-Hakeem, Mohamed S. ; He, Zhong ; Procopio, Francesco Andrea ; Shi, Yu ; Haddad, Elias K. ; Ancuta, Petronela ; Sekaly, Rafick Pierre ; Said, Elias A. / HCV RNA Activates APCs via TLR7/TLR8 while Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses. In: Scientific Reports. 2016 ; Vol. 6.
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