کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3346393 1215784 2008 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The sweetness of the DNA backbone drives Toll-like receptor 9
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
The sweetness of the DNA backbone drives Toll-like receptor 9
چکیده انگلیسی

The prevailing paradigm ascribes activation of Toll-like receptor 9 (TLR9) to the detection of CpG-motifs within pathogen derived DNA. However, new work ties natural phospho-diester (PD) DNA recognition by TLR9 to the detection of the DNA sugar backbone 2′ deoxyribose. PD 2′ deoxyribose homopolymers lacking DNA bases (abasic) are shown to act as TLR9 agonist while abasic phospho-thioate (PS) 2′ deoxyribose functions as TLR9 antagonist. Alignment of bases to PD 2′ deoxyribose enhanced its TLR9 agonistic function, while only CpG-motifs introduced to inhibitory PS 2′ deoxyribose converted the antagonistic activity into powerful agonistic function. These new data thus restrict the CpG-motif dependency of TLR9 activation to the promising group of immunopharmacons that are based on PS modified synthetic DNA. They also show that natural PD DNA drives TLR9 activation sequence-independently as is the case for ds RNA recognizing TLR3 and ss RNA recognizing TLR7 and TLR8. Thus evolutionary pressure might have exiled nucleic acid recognizing TLRs such as TLR9 to endosomes in order to avoid activation by host (self) derived nucleic acids.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Current Opinion in Immunology - Volume 20, Issue 4, August 2008, Pages 396–400
نویسندگان
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