TITLE

The Two-Component Adjuvant IC31® Boosts Type I Interferon Production of Human Monocyte-Derived Dendritic Cells via Ligation of Endosomal TLRs

AUTHOR(S)
Szabo, Attila; Gogolak, Peter; Pazmandi, Kitti; Kis-Toth, Katalin; Riedl, Karin; Wizel, Benjamin; Lingnau, Karen; Bacsi, Attila; Rethi, Bence; Rajnavolgyi, Eva
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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.
ACCESSION #
87623660

 

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