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• W1590649050 abstract "Liquid-crystalline arrangements of complexes of DNA and antimicrobial peptides can lead to multivalent electrostatic interactions that drastically amplify TLR9-mediated immune responses. Double-stranded DNA (dsDNA) can trigger the production of type I interferon (IFN) in plasmacytoid dendritic cells (pDCs) by binding to endosomal Toll-like receptor-9 (TLR9; refs 1, 2, 3, 4, 5). It is also known that the formation of DNA–antimicrobial peptide complexes can lead to autoimmune diseases via amplification of pDC activation1,2. Here, by combining X-ray scattering, computer simulations, microscopy and measurements of pDC IFN production, we demonstrate that a broad range of antimicrobial peptides and other cationic molecules cause similar effects, and elucidate the criteria for amplification. TLR9 activation depends on both the inter-DNA spacing and the multiplicity of parallel DNA ligands in the self-assembled liquid-crystalline complex. Complexes with a grill-like arrangement of DNA at the optimum spacing can interlock with multiple TLR9 like a zipper, leading to multivalent electrostatic interactions that drastically amplify binding and thereby the immune response. Our results suggest that TLR9 activation and thus TLR9-mediated immune responses can be modulated deterministically." @default.
• W1590649050 created "2016-06-24" @default.
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• W1590649050 date "2015-06-08" @default.
• W1590649050 modified "2023-10-12" @default.
• W1590649050 title "Liquid-crystalline ordering of antimicrobial peptide–DNA complexes controls TLR9 activation" @default.
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• W1590649050 doi "https://doi.org/10.1038/nmat4298" @default.
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