title: The TLR-independent DNA recognition pathway in murine macrophages: Ligand features and molecular signature.
abstract: Recognition of foreign DNA by cytosolic innate immune receptors triggers the production of IFN-beta. However, it is unclear whether different types of DNA ligands are recognized by similar receptors and whether the resulting response is distinct from the endosomal TLR response. To address these questions, we compared the two most commonly used types of DNA ligands (IFN-stimulatory DNA (ISD) and poly(dAdT)) and assessed the minimal structural requirements for stimulatory capacity in RAW264.7 cells. Gene expression signatures and competition experiments suggest that ISD and poly(dAdT) are qualitatively indistinguishable and differ from the CpG-containing oligonucleotides triggering the TLR9 pathway. Structure - activity relationship analyses revealed that a minimal length of two helical turns is sufficient for ISD-mediated IFN-beta induction, while phosphorylation at the 5'-end is dispensable. Altogether, our data suggest that, in murine macrophages, only one major cytosolic DNA recognition pathway is operational.
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Evren
authors: E
authors: Karayel
authors: Tilmann
authors: T
authors: Bürckstümmer
authors: Martin
authors: M
authors: Bilban
authors: Gerhard
authors: G
authors: Dürnberger
authors: Stefan
authors: S
authors: Weitzer
authors: Javier
authors: J
authors: Martinez
authors: Giulio
authors: G
authors: Superti-Furga
mesh_terms: D000818:Animals; D002460:Cell Line; D054371:Chemokine CXCL11 / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D015151:Immunoblotting; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000235:genetics; D010766:Phosphorylation; D011067:Poly dA-dT / Q000235:genetics; D011506:Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics; D015398:Signal Transduction; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D014162:Transfection
chemical_list: D054371:Chemokine CXCL11; C515203:Cxcl11 protein, mouse; C087697:Ifit3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D009841:Oligonucleotides; D011506:Proteins; D015843:Serpins; C092499:Tgtp protein, mouse; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D011067:Poly dA-dT; D016899:Interferon-beta; D004247:DNA; D020559:Monomeric GTP-Binding Proteins