The Two-component Adjuvant IC31® Boosts Type I Interferon Production of Human Monocyte-derived Dendritic Cells Via Ligation of Endosomal TLRs

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Feb 14

PMID 23405128

Citations 13

Authors

Attila Szabo

Peter Gogolak

Kitti Pazmandi

Katalin Kis-Toth

Karin Riedl

Benjamin Wizel

Karen Lingnau

Attila Bacsi

Bence Rethi

Eva Rajnavolgyi

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to characterize and identify the mode of action of IC31®, a two-component vaccine adjuvant. We found that IC31® was accumulated in human peripheral blood monocytes, MHC class II positive cells and monocyte-derived DCs (moDCs) but not in plasmacytoid DCs (pDCs). In the presence of IC31® the differentiation of inflammatory CD1a(+) moDCs and the secretion of chemokines, TNF-α and IL-6 cytokines was inhibited but the production of IFNβ was increased. Sustained addition of IC31® to differentiating moDCs interfered with IκBα phosphorylation, while the level of phospho-IRF3 increased. We also showed that both IC31® and its KLK component exhibited a booster effect on type I IFN responses induced by the specific ligands of TLR3 or TLR7/8, whereas TLR9 ligand induces type I IFN production only in the presence of IC31® or ODN1. Furthermore, long term incubation of moDCs with IC31® caused significantly higher expression of IRF and IFN genes than a single 24 hr treatment. The adjuvant activity of IC31® on the IFN response was shown to be exerted through TLRs residing in the vesicular compartment of moDCs. Based on these results IC31® was identified as a moDC modulatory adjuvant that sets the balance of the NF-κB and IRF3 mediated signaling pathways to the production of IFNβ. Thus IC31® is emerging as a potent adjuvant to increase immune responses against intracellular pathogens and cancer in future vaccination strategies.

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