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Plos One : the Two-component Adjuvant Ic31® Boosts Type I Interferon Production of Human Monocyte-derived Dendritic Cells Via Ligation of Endosomal Tlrs, Volume 7

By Marques, Ernesto, T. A.

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Book Id: WPLBN0003961574
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : the Two-component Adjuvant Ic31® Boosts Type I Interferon Production of Human Monocyte-derived Dendritic Cells Via Ligation of Endosomal Tlrs, Volume 7  
Author: Marques, Ernesto, T. A.
Volume: Volume 7
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Historic
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Publisher: Plos

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A. Marque, E. T. (n.d.). Plos One : the Two-component Adjuvant Ic31® Boosts Type I Interferon Production of Human Monocyte-derived Dendritic Cells Via Ligation of Endosomal Tlrs, Volume 7. Retrieved from http://netlibrary.net/


Description
Description : The aim of this study was to characterize and identify the mode of action of IC31H, a two-component vaccine adjuvant. We found that IC31H 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 IC31H the differentiation of inflammatory CD1a+ moDCs and the secretion of chemokines, TNF-a and IL-6 cytokines was inhibited but the production of IFNb was increased. Sustained addition of IC31H to differentiating moDCs interfered with IkBa phosphorylation, while the level of phospho-IRF3 increased. We also showed that both IC31H 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 IC31H or ODN1. Furthermore, long term incubation of moDCs with IC31H caused significantly higher expression of IRF and IFN genes than a single 24 hr treatment. The adjuvant activity of IC31H on the IFN response was shown to be exerted through TLRs residing in the vesicular compartment of moDCs. Based on these results IC31H was identified as a moDC modulatory adjuvant that sets the balance of the NF-kB and IRF3 mediated signaling pathways to the production of IFNb. Thus IC31H is emerging as a potent adjuvant to increase immune responses against intracellular pathogens and cancer in future vaccination strategies.

 

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