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PLoS One. 2013;8(2):e55264. doi: 10.1371/journal.pone.0055264. Epub 2013 Feb 6.

The two-component adjuvant IC31® boosts type i interferon production of human monocyte-derived dendritic cells via ligation of endosomal TLRs.

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1
Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary.

Erratum in

  • PLoS One. 2013;8(10). doi:10.1371/annotation/322893f7-942c-4059-9295-7ecd26162aca.

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.

PMID:
23405128
PMCID:
PMC3566214
DOI:
10.1371/journal.pone.0055264
[Indexed for MEDLINE]
Free PMC Article
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