title: Polyinosinic acid is a ligand for toll-like receptor 3.
abstract: Innate immune responses are critical in controlling viral infections. Viral proteins and nucleic acids have been shown to be recognized by pattern recognition receptors of the Toll-like receptor (TLR) family, triggering downstream signaling cascades that lead to cellular activation and cytokine production. Viral DNA is sensed by TLR9, and TLRs 3, 7, and 8 have been implicated in innate responses to RNA viruses by virtue of their ability to sense double-stranded (ds) RNA (TLR3) or single-stranded RNA (murine TLR7 and human TLR8). Viral and synthetic dsRNAs have also been shown to be a potent adjuvant, promoting enhanced adaptive immune responses, and this property is also dependent on their recognition by TLR3. It has recently been shown that mRNA that is largely single-stranded is a ligand for TLR3. Here we have investigated the ability of single-stranded homopolymeric nucleic acids to induce innate responses by murine immune cells. We show for the first time that polyinosinic acid (poly(I)) activates B lymphocytes, dendritic cells, and macrophages and that these responses are dependent on the expression of both TLR3 and the adaptor molecule, Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF). We therefore conclude that TLR3 is able to sense both single-stranded RNA and dsRNA.
authors.affiliation: Department of Human Anatomy and Cell Biology, The University of Liverpool, Liverpool L69 3GE, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Marshall-Clarke
authors.forename: Joan E
authors.initials: JE
authors.lastname: Downes
authors.forename: Ismar R
authors.initials: IR
authors.lastname: Haga
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Bowie
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Pennock
authors.forename: Richard K
authors.initials: RK
authors.lastname: Grencis
authors.forename: Paul
authors.initials: P
authors.lastname: Rothwell
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001980:Bronchi / Q000166:cytology; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011069:Poly I / Q000378:metabolism*; D012313:RNA / Q000737:chemistry*; D012330:RNA, Double-Stranded / Q000737:chemistry*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*
chemical_list: D008024:Ligands; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3; D011069:Poly I; D012313:RNA