Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 39, Issue 7, Pages 1929-1936Publisher
WILEY
DOI: 10.1002/eji.200939344
Keywords
Cytosolic DNA recognition; IFN-beta; IFN-stimulatory DNA; Innate immunity
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Funding
- Austrian Ministry of Education and Research [GZ200.145/1-VI/I/2006, GZ200.142/1-VI/I/2006]
- Austrian Science Fund [FWF W1205]
- Austrian Science Fund (FWF) [W1207] Funding Source: Austrian Science Fund (FWF)
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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.
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