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

Citation:
Zhang, Y., M. El-Far, F. P. Dupuy, M. S. Abdel-Hakeem, Z. He, F. A. Procopio, Y. Shi, E. K. Haddad, P. Ancuta, R. - P. Sekaly, et al., "HCV RNA Activates APCs via TLR7/TLR8 While Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses.", Scientific Reports, vol. 6, pp. 1-13, 2016.

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 proinflammatory
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.

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DOI:

10.1038/srep29447

PMID:

27385120

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