In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 86, No. 3 ( 2009-07-20), p. 663-670
Abstract:
Mammalian genomic DNA complexed to the natural antimicrobial cationic peptide LL37 induces type I interferon but less than bacterial DNA or CG-dinucleotide containing oligodeoxynucleotides. TLR9 detects DNA in endolysosomal compartments of human B cells and PDC. Recently, the concept of the CpG motif specificity of TLR9-mediated detection, specifically of natural phosphodiester DNA, has been challenged. Unlike in human B cells, CpG specificity of natural phosphodiester DNA recognition in human PDC has not been analyzed in the literature. Here, we found that the induction of IFN-α and TNF-α in human PDC by phosphodiester ODNs containing one or two CG dinucleotides was reduced to a lower level when the CG dinucleotides were methylated and was abolished if the CGs were switched to GCs. Consistent with a high frequency of unmethylated CG dinucleotides, bacterial DNA induced high levels of IFN-α in PDC; IFN-α was reduced but not abolished upon methylation of bacterial DNA. Mammalian DNA containing low numbers of CG dinucleotides, which are frequently methylated, induced IFN-α in PDC consistently but on a much lower level than bacterial DNA. For activation of PDC, phosphodiester ODNs and genomic DNA strictly required complexation with cationic molecules such as the keratinocyte-derived antimicrobial peptide LL37 or a scrambled derivative. In conclusion, we demonstrate that self-DNA complexed to cationic molecules activate PDC and thus, indeed, may function as DAMPs; nevertheless, the preference of PDC for CpG containing DNA provides the basis for the discrimination of microbial from self-DNA even if DNA is presented in the condensed form of a complex.
Type of Medium:
Online Resource
ISSN:
1938-3673
,
0741-5400
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2009
detail.hit.zdb_id:
2026833-6
SSG:
12
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