TY - JOUR
T1 - HCV RNA Activates APCs via TLR7/TLR8 while Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses
AU - Zhang, Yuwei
AU - El-Far, Mohamed
AU - Dupuy, Franck P.
AU - Abdel-Hakeem, Mohamed S.
AU - He, Zhong
AU - Procopio, Francesco Andrea
AU - Shi, Yu
AU - Haddad, Elias K.
AU - Ancuta, Petronela
AU - Sekaly, Rafick Pierre
AU - Said, Elias A.
PY - 2016/7/7
Y1 - 2016/7/7
N2 - 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.
AB - 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.
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U2 - 10.1038/srep29447
DO - 10.1038/srep29447
M3 - Article
C2 - 27385120
AN - SCOPUS:84978116776
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 29447
ER -