title: Adjuvating the adjuvant: facilitated delivery of an immunomodulatory oligonucleotide to TLR9 by a cationic antimicrobial peptide in dendritic cells.
abstract: IC31(®) is a novel bi-component vaccine adjuvant consisting of the peptide KLKL(5)KLK (KLK) and the TLR9 agonist oligonucleotide d(IC)(13) (ODN1a). While membrane-interacting properties of KLK and immuno-modulating capabilities of ODN1a have been characterized in detail, little is known of how these two molecules function together and synergize in interacting with their primary target cells, dendritic cells (DCs). We have found that KLK-triggered aggregates entrapped ODN1a and these complexes readily associated with the DC cell surface. KLK stimulated the uptake and internalization of ODN1a via endocytosis, while the bulk of the peptide remained associated with the cell periphery. ODN1a co-localized with early and late endosomes as well as endoplasmic reticular structures. ODN1a co-localized with TLR9 positive compartments following KLK mediated uptake. These features did not depend on the expression of TLR-9. Our results reveal novel mechanisms that allow KLK to enhance the effects of the TLR-9 ligand ODN1a in immunomodulation.
authors.affiliation: Department of Genetics, Max F. Perutz Laboratories, Dr. Bohrgasse 9, 1030 Vienna, Austria.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Aichinger
authors.forename: Michael
authors.initials: M
authors.lastname: Ginzler
authors.forename: Julian
authors.initials: J
authors.lastname: Weghuber
authors.forename: Lars
authors.initials: L
authors.lastname: Zimmermann
authors.forename: Karin
authors.initials: K
authors.lastname: Riedl
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schütz
authors.forename: Eszter
authors.initials: E
authors.lastname: Nagy
authors.forename: Alexander
authors.initials: A
authors.lastname: von Gabain
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schweyen
authors.forename: Tamás
authors.initials: T
authors.lastname: Henics
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004338:Drug Combinations; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000737:chemistry; D011992:Endosomes / Q000737:chemistry; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*; D009841:Oligonucleotides / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D023181:Antimicrobial Cationic Peptides; D004338:Drug Combinations; C544002:IC31 adjuvant; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D009842:Oligopeptides; D051217:Toll-Like Receptor 9