title: IFNs activate toll-like receptor gene expression in viral infections.
abstract: Toll-like receptors (TLRs) mediate innate immune responses to microbes. TLR2, TLR5, TLR6, and TLR9 have been implicated in responses to bacterial components, and TLR4 is the receptor for Gram-negative bacteria. Recently, TLR4 was described to function in respiratory syncytial virus-induced NF-kappaB activation. Here we have analyzed TLR1-9 mRNA expression in human primary macrophages infected with influenza A and Sendai viruses. TLR1, TLR2, TLR4, TLR6, and TLR8 mRNAs were expressed at basal levels in macrophages. Viral infection enhanced TLR1, TLR2, TLR3, and TLR7 mRNA expression, and neutralizing anti-IFN-alpha/beta antibodies downregulated gene expression of these TLRs. Exogenously added IFN-alpha upregulated TLR1, TLR2, TLR3, and TLR7 mRNA expression in macrophages, as well as TLR3 mRNA expression in epithelial and endothelial cell lines. IFN-gamma enhanced the expression of TLR1 and TLR2 mRNA in macrophages, and TLR3 in epithelial and endothelial cells. The data suggests a novel role for IFNs in the activation of innate immunity.
authors.affiliation: Department of Microbiology, National Public Health Institute, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Miettinen
authors.forename: T
authors.initials: T
authors.lastname: Sareneva
authors.forename: I
authors.initials: I
authors.lastname: Julkunen
authors.forename: S
authors.initials: S
authors.lastname: Matikainen
mesh_terms: D000906:Antibodies / Q000276:immunology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D007372:Interferons / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000821:virology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029082:Sendai virus / Q000502:physiology*; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D015854:Up-Regulation
chemical_list: D000906:Antibodies; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; C495346:TLR5 protein, human; C495348:TLR7 protein, human; C495349:TLR8 protein, human; C495371:TLR9 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D007372:Interferons