%0 Journal Article
%T The Two-Component Adjuvant IC31£¿ Boosts Type I Interferon Production of Human Monocyte-Derived Dendritic Cells via Ligation of Endosomal TLRs
%A Attila Szabo
%A Peter Gogolak
%A Kitti Pazmandi
%A Katalin Kis-Toth
%A Karin Riedl
%A Benjamin Wizel
%A Karen Lingnau
%A Attila Bacsi
%A Bence Rethi
%A Eva Rajnavolgyi
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0055264
%X 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-¦Á and IL-6 cytokines was inhibited but the production of IFN¦Â was increased. Sustained addition of IC31£¿ to differentiating moDCs interfered with I¦ÊB¦Á 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-¦ÊB and IRF3 mediated signaling pathways to the production of IFN¦Â. Thus IC31£¿ is emerging as a potent adjuvant to increase immune responses against intracellular pathogens and cancer in future vaccination strategies.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0055264