Title

The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling

PubMed ID

15695821

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Date

2-8-2005

Document Type

Article

Subjects

Adaptor Proteins, Signal Transducing; Antigens, Differentiation; Biological Assay; Cell Line; DNA-Binding Proteins; Dose-Response Relationship, Drug; Electroporation; Genes, Reporter; Glutathione Transferase; Humans; Interferon Regulatory Factor-3; Interferon Regulatory Factor-7; Interferon Regulatory Factors; Interferon Type I; Ligands; Lipopolysaccharides; Membrane Glycoproteins; Microscopy, Confocal; Models, Biological; Myeloid Differentiation Factor 88; Phosphorylation; RNA Interference; RNA, Double-Stranded; RNA, Small Interfering; Receptors, Cell Surface; Receptors, Immunologic; Recombinant Fusion Proteins; Reverse Transcriptase Polymerase Chain Reaction; *Signal Transduction; Time Factors; Toll-Like Receptor 3; Toll-Like Receptor 4; Toll-Like Receptor 7; Toll-Like Receptor 8; Toll-Like Receptors; Transcription Factors; Transfection

Disciplines

Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences

Abstract

Interferon regulatory factors (IRFs) are critical components of virus-induced immune activation and type I interferon regulation. IRF3 and IRF7 are activated in response to a variety of viruses or after engagement of Toll-like receptor (TLR) 3 and TLR4 by double-stranded RNA and lipopolysaccharide, respectively. The activation of IRF5, is much more restricted. Here we show that in contrast to IRF3 and IRF7, IRF5 is not a target of the TLR3 signaling pathway but is activated by TLR7 or TLR8 signaling. We also demonstrate that MyD88, interleukin 1 receptor-associated kinase 1, and tumor necrosis factor receptor-associated factor 6 are required for the activation of IRF5 and IRF7 in the TLR7 signaling pathway. Moreover, ectopic expression of IRF5 enabled type I interferon production in response to TLR7 signaling, whereas knockdown of IRF5 by small interfering RNA reduced type I interferon induction in response to the TLR7 ligand, R-848. IRF5 and IRF7, therefore, emerge from these studies as critical mediators of TLR7 signaling.

Rights and Permissions

Citation: J Biol Chem. 2005 Apr 29;280(17):17005-12. Epub 2005 Jan 28. Link to article on publisher's site

Related Resources

Link to Article in PubMed