title: HCV RNA Activates APCs via TLR7/TLR8 While Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses.
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.
authors.affiliation: Centre de recherche du centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital Saint-Luc, Québec H2X 0A9, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.|Vaccine and Gene Therapy Institute-Florida (VGTI-FL), Port Saint Lucie, Florida 3498, USA.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Centre de recherche du centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital Saint-Luc, Québec H2X 0A9, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Far
authors.affiliation: Centre de recherche du centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital Saint-Luc, Québec H2X 0A9, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.|Vaccine and Gene Therapy Institute-Florida (VGTI-FL), Port Saint Lucie, Florida 3498, USA.|Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Franck P
authors.initials: FP
authors.lastname: Dupuy
authors.affiliation: Centre de recherche du centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital Saint-Luc, Québec H2X 0A9, Canada.|Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo 11562, Egypt.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Abdel-Hakeem
authors.affiliation: Centre de recherche du centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital Saint-Luc, Québec H2X 0A9, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.|Vaccine and Gene Therapy Institute-Florida (VGTI-FL), Port Saint Lucie, Florida 3498, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: He
authors.affiliation: Centre de recherche du centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital Saint-Luc, Québec H2X 0A9, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.|Vaccine and Gene Therapy Institute-Florida (VGTI-FL), Port Saint Lucie, Florida 3498, USA.
authors.forename: Francesco Andrea
authors.initials: FA
authors.lastname: Procopio
authors.affiliation: Centre de recherche du centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital Saint-Luc, Québec H2X 0A9, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.|Vaccine and Gene Therapy Institute-Florida (VGTI-FL), Port Saint Lucie, Florida 3498, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Centre de recherche du centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital Saint-Luc, Québec H2X 0A9, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.|Vaccine and Gene Therapy Institute-Florida (VGTI-FL), Port Saint Lucie, Florida 3498, USA.
authors.forename: Elias K
authors.initials: EK
authors.lastname: Haddad
authors.affiliation: Centre de recherche du centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital Saint-Luc, Québec H2X 0A9, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.
authors.forename: Petronela
authors.initials: P
authors.lastname: Ancuta
authors.affiliation: Centre de recherche du centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital Saint-Luc, Québec H2X 0A9, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.|Vaccine and Gene Therapy Institute-Florida (VGTI-FL), Port Saint Lucie, Florida 3498, USA.|Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sekaly
authors.affiliation: Centre de recherche du centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital Saint-Luc, Québec H2X 0A9, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.|Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, the Sultanate of Oman.
authors.forename: Elias A
authors.initials: EA
authors.lastname: Said
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology / Q000821:virology*; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D057809:HEK293 Cells; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D012367:RNA, Viral / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D051200:Toll-Like Receptor 8 / Q000378:metabolism*
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D012367:RNA, Viral; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D002738:Chloroquine