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  • Liquid-crystalline ordering of antimicrobial peptide-DNA complexes controls TLR9 activation [Elektronski vir]
    Schmidt, Nathan W. ...
    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.
    Vir: Nature Materials [Elektronski vir]. - ISSN 1476-4660 (Vol. 14, 2015, str. 696-700)
    Vrsta gradiva - e-članek ; neleposlovje za odrasle
    Leto - 2015
    Jezik - angleški
    COBISS.SI-ID - 525410585

    Povezava(-e):

    http://www.nature.com/nmat/journal/v14/n7/full/nmat4298.html

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