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

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15 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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    Zhang, Y., El-Far, M., Dupuy, F. P., Abdel-Hakeem, M. S., He, Z., Procopio, F. A., Shi, Y., Haddad, E. K., Ancuta, P., Sekaly, R. P., & Said, E. A. (2016). HCV RNA Activates APCs via TLR7/TLR8 while Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses. Scientific Reports, 6, [29447]. https://doi.org/10.1038/srep29447