Adjuvating the adjuvant: Facilitated delivery of an immunomodulatory oligonucleotide to TLR9 by a cationic antimicrobial peptide in dendritic cells

Michael C. Aichinger, Michael Ginzler, Julian Weghuber, Lars Zimmermann, Karin Riedl, Gerhard Schütz, Eszter Nagy, Alexander von Gabain, Rudolf Schweyen, Tamás Henics

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

IC31® is a novel bi-component vaccine adjuvant consisting of the peptide KLKL5KLK (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.

Original languageEnglish
Pages (from-to)426-436
Number of pages11
JournalVaccine
Volume29
Issue number3
DOIs
Publication statusPublished - 10 Jan 2011

Keywords

  • Adjuvant
  • Cationic antimicrobial peptide
  • Dendritic cell
  • Endoplasmic Reticulum/chemistry
  • Oligodeoxyribonucleotides/metabolism
  • Humans
  • Mice, Inbred C57BL
  • Cells, Cultured
  • Oligopeptides/metabolism
  • Endosomes/chemistry
  • Toll-Like Receptor 9/metabolism
  • Oligonucleotides/metabolism
  • Endocytosis
  • Animals
  • Antimicrobial Cationic Peptides/metabolism
  • Adjuvants, Immunologic/metabolism
  • Dendritic Cells/immunology
  • Mice
  • Drug Combinations

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