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

• Published in: Vaccine Vol. 29; no. 3; pp. 426 - 436
• Main Authors: Aichinger, Michael C, Ginzler, Michael, Weghuber, Julian, Zimmermann, Lars, Riedl, Karin, Schütz, Gerhard, Nagy, Eszter, von Gabain, Alexander, Schweyen, Rudolf, Henics, Tamás
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 10.01.2011; Elsevier; Elsevier Limited
• Subjects: Adjuvant; Adjuvants, Immunologic - metabolism; agonists; Allergy and Immunology; Animals; Antimicrobial Cationic Peptides - metabolism; antimicrobial peptides; Applied microbiology; Biological and medical sciences; Bone marrow; Cationic antimicrobial peptide; Cells, Cultured; Dendritic cell; dendritic cells; Dendritic Cells - immunology; Drug Combinations; Endocytosis; Endoplasmic Reticulum - chemistry; endosomes; Endosomes - chemistry; Experiments; Fundamental and applied biological sciences. Psychology; Humans; Immune system; immunomodulation; Laboratory animals; Ligands; Lymphocytes; Mice; Mice, Inbred C57BL; Microbiology; Oligodeoxyribonucleotides - metabolism; oligonucleotides; Oligonucleotides - metabolism; Oligopeptides - metabolism; Peptides; Toll-Like Receptor 9 - metabolism; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Austria; Dendritic cell; Cationic antimicrobial peptide; Adjuvant; Peptides; Immunological adjuvant; Antimicrobial agent
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.11.003

Abstract IC31® is a novel bi-component vaccine adjuvant consisting of the peptide KLKL5 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.