title: Complexes of DNA with the Antimicrobial Peptide LL37 Augment NK Cell Functions by Inducing Type I Interferon Production from Circulating Monocytes and Plasmacytoid Predendritic Cells.
abstract: The cationic antimicrobial peptide, LL37, forms electrostatic complexes with DNA (LL37-DNA), which are potent activators of circulating plasmacytoid predendritic cells (ppDCs) and monocytes. However, the effects of LL37-DNA on other immune cell types, such as NK cells, are poorly characterized. In this study, we show that complexes of human genomic DNA (hgDNA) or synthetic double-stranded oligodeoxynucleotides with LL37 strongly enhance natural cytotoxicity of human peripheral blood mononuclear cells (PBMCs) upon an overnight culture, whereas hgDNA alone has no effect, and LL37 alone is moderately active. LL37-DNA complexes potentiate degranulation of, and interferon (IFN)-γ production by, NK cells upon subsequent encounter of K562 target cells. The complexes do not influence percentages of NK cells among PBMCs or the expression of cytotoxic proteins by NK cells. Using neutralizing anticytokine antibodies and immunomagnetic depletion of different subpopulations of PBMCs, we found that the effect of LL37-DNA on NK cells is indirect and mediated by type I IFNs produced by monocytes and, to a lesser extent, by ppDCs. We discuss possible roles of LL37-DNA complexes in the regulation of NK cell functions and in the treatment of cancer.
authors.affiliation: 1 Laboratory of Clinical Immunology, National Research Center-Institute of Immunology of the Federal Medical-Biological Agency , Moscow, Russia .
authors.forename: Boris V
authors.initials: BV
authors.lastname: Pinegin
authors.affiliation: 1 Laboratory of Clinical Immunology, National Research Center-Institute of Immunology of the Federal Medical-Biological Agency , Moscow, Russia .
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Pashenkov
authors.affiliation: 1 Laboratory of Clinical Immunology, National Research Center-Institute of Immunology of the Federal Medical-Biological Agency , Moscow, Russia .
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Kulakov
authors.affiliation: 1 Laboratory of Clinical Immunology, National Research Center-Institute of Immunology of the Federal Medical-Biological Agency , Moscow, Russia .
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Murugin
authors.affiliation: 2 Laboratory of Ligand-Receptor Interactions, M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bio-Organic Chemistry of the Russian Academy of Sciences , Moscow, Russia .
authors.forename: Maxim N
authors.initials: MN
authors.lastname: Zhmak
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000378:metabolism*; D015550:Cell Degranulation / Q000276:immunology; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D007370:Interferon Type I; D007371:Interferon-gamma; D004247:DNA