title: Porcine cathelicidins efficiently complex and deliver nucleic acids to plasmacytoid dendritic cells and can thereby mediate bacteria-induced IFN-α responses.
abstract: Cathelicidins constitute potent antimicrobial peptides characterized by a high cationic charge that enables strong interactions with nucleic acids. In fact, the only human cathelicidin LL-37 triggers rapid sensing of nucleic acids by plasmacytoid dendritic cells (pDC). Among the porcine cathelicidins, phylogenetic analysis of the C-terminal mature peptide showed that porcine myeloid antimicrobial peptide (PMAP)-36 was the most closely related of the 11 porcine cathelicidins to human LL-37. Despite several investigations evaluating potent antimicrobial functions of porcine cathelicidins, nothing is known about their ability to promote pDC activation. We therefore investigated the capacity of the proline-arginine-rich 39-aa peptide, PMAP-23, PMAP-36, and protegrin-1 to complex with bacterial DNA or synthetic RNA molecules and facilitate pDC activation. We demonstrate that these peptides mediate a rapid and efficient uptake of nucleic acids within minutes, followed by robust IFN-α responses. The highest positively charged cathelicidin, PMAP-36, was found to be the most potent peptide tested for this effect. The peptide-DNA complexes were internalized and also found to associate with the cell membranes of pDC. The amphipathic conformation typical of PMAP-36 was not required for IFN-α induction in pDC. We also demonstrate that PMAP-36 can mediate IFN-α induction in pDC stimulated by Escherichia coli, which alone fail to activate pDC. This response was weaker with a scrambled PMAP-36, relating to its lower antimicrobial activity. Collectively, our data suggest that the antimicrobial and nucleic acid-complexing properties of cathelicidins can mediate pDC activation-promoting adaptive immune responses against microbial infections.
authors.affiliation: Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland; and Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Baumann
authors.affiliation: Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Démoulins
authors.affiliation: Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland; and.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Python
authors.affiliation: Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland; and artur.summerfield@ivi.admin.ch.
authors.forename: Artur
authors.initials: A
authors.lastname: Summerfield
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology* / Q000473:pathology; D004269:DNA, Bacterial / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D017433:Protein Structure, Secondary; D013552:Swine; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D004269:DNA, Bacterial; D016898:Interferon-alpha; D054804:Cathelicidins