title: TLR3 activation efficiency by high or low molecular mass poly I:C.
abstract: Toll-like receptor 3 (TLR3) plays a critical role in initiating type I IFN-mediated innate immunity against viral infections. TLR3 recognizes various forms of double stranded (ds) RNA, including viral dsRNA and a synthetic mimic of dsRNA, poly I:C, which has been used extensively as a TLR3 ligand to induce antiviral immunity. The activation efficiency of TLR3 by poly I:C is influenced by various factors, including size of the ligands, delivery methods and cell types. In this study, we examined the stimulatory effect of two commercially-available poly I:Cs [high molecular mass (HMM) and low molecular mass (LMM)] on TLR3 activation in various human cell types by determining the induction of type I and type III IFNs, as well as the antiviral effect. We demonstrated that the direct addition of both HMM- and LMM-poly I:C to the cultures of primary macrophages or a neuroplastoma cell line could activate TLR3. However, the transfection of poly I:C was necessary to induce TLR3 activation in other cell types studied. In all the cell lines tested, the efficiency of TLR3 activation by HMM-poly I:C was significantly higher than that by LMM-poly I:C. These observations indicate the importance and necessity of developing effective TLR3 ligands for antiviral therapy.
authors.affiliation: Center for Animal Experiment/Animal Biosafety Level III Laboratory and State Key Laboratory of Virology, Wuhan University School of Medicine, Wuhan, Hubei, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ming
authors.initials: M
authors.lastname: Guo
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Jielang
authors.initials: J
authors.lastname: Li
authors.forename: Yizhong
authors.initials: Y
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Ming
authors.initials: M
authors.lastname: Dai
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Yuri
authors.initials: Y
authors.lastname: Persidsky
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ho
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D022781:Hepatocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D008970:Molecular Weight; D009447:Neuroblastoma / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D011070:Poly I-C / Q000737:chemistry / Q000494:pharmacology*; D012367:RNA, Viral / Q000032:analysis / Q000737:chemistry; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D014777:Virus Diseases / Q000276:immunology*; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; D011070:Poly I-C; D012367:RNA, Viral; D051196:Toll-Like Receptor 3; C000624353:interferon-lambda, human; D000095022:Interferon Lambda