title: Chicken toll-like receptor 3 recognizes its cognate ligand when ectopically expressed in human cells.
abstract: Recognition of pathogens by toll-like receptors (TLRs) causes activation of signaling cascades that trigger cytokine secretion and, ultimately, innate immunity. Genes encoding proteins with substantial homology to mammalian TLR1, TLR2, TLR3, TLR4, TLR5, and TLR7 are present in the chicken genome, whereas orthologs of TLR8, TLR9, and TLR10 seem to be defective or missing. Except for chicken TLR2 (ChTLR2), which was previously shown to recognize lipopeptides and lipopolysaccharides (LPS), the ligand specificity of ChTLRs had not been determined. We found that polyI:C, LPS, R848, S-28463, and ODN2006, which are specifically recognized by TLR3, TLR4, TLR7/8, and TLR9 in mammals, induced substantial amounts of type I interferon (IFN) and interleukin-6 (IL-6) in freshly prepared chicken splenocytes. To determine the ligand specificity of ChTLR3 and ChTLR7, we used a standard reporter assay frequently employed for analysis of mammalian TLRs. Neither S-28463 nor any other TLR ligand induced reporter activity in human 293 cells expressing ChTLR7. However, human 293 cells expressing ChTLR3 strongly and specifically responded to polyI:C, demonstrating that this chicken receptor represents a true ortholog of mammalian TLR3.
authors.affiliation: Department of Virology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Schwarz
authors.forename: Kirsten
authors.initials: K
authors.lastname: Schneider
authors.forename: Annette
authors.initials: A
authors.lastname: Ohnemus
authors.forename: Miha
authors.initials: M
authors.lastname: Lavric
authors.forename: Sonja
authors.initials: S
authors.lastname: Kothlow
authors.forename: Stefan
authors.initials: S
authors.lastname: Bauer
authors.forename: Bernd
authors.initials: B
authors.lastname: Kaspers
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D007369:Interferon Inducers; D007370:Interferon Type I; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D011070:Poly I-C