The two-component adjuvant IC31® boosts type i interferon production of human monocyte-derived dendritic cells via ligation of endosomal TLRs.
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 prese...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3566214?pdf=render |
| _version_ | 1818423254550839296 |
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| author | Attila Szabo Peter Gogolak Kitti Pazmandi Katalin Kis-Toth Karin Riedl Benjamin Wizel Karen Lingnau Attila Bacsi Bence Rethi Eva Rajnavolgyi |
| author_facet | Attila Szabo Peter Gogolak Kitti Pazmandi Katalin Kis-Toth Karin Riedl Benjamin Wizel Karen Lingnau Attila Bacsi Bence Rethi Eva Rajnavolgyi |
| author_sort | Attila Szabo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T13:39:14Z |
| format | Article |
| id | doaj.art-9dbe321337934cf3b936c18e5564d108 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T13:39:14Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9dbe321337934cf3b936c18e5564d1082022-12-21T22:59:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5526410.1371/journal.pone.0055264The two-component adjuvant IC31® boosts type i interferon production of human monocyte-derived dendritic cells via ligation of endosomal TLRs.Attila SzaboPeter GogolakKitti PazmandiKatalin Kis-TothKarin RiedlBenjamin WizelKaren LingnauAttila BacsiBence RethiEva RajnavolgyiThe 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.http://europepmc.org/articles/PMC3566214?pdf=render |
| spellingShingle | Attila Szabo Peter Gogolak Kitti Pazmandi Katalin Kis-Toth Karin Riedl Benjamin Wizel Karen Lingnau Attila Bacsi Bence Rethi Eva Rajnavolgyi The two-component adjuvant IC31® boosts type i interferon production of human monocyte-derived dendritic cells via ligation of endosomal TLRs. PLoS ONE |
| title | The two-component adjuvant IC31® boosts type i interferon production of human monocyte-derived dendritic cells via ligation of endosomal TLRs. |
| title_full | The two-component adjuvant IC31® boosts type i interferon production of human monocyte-derived dendritic cells via ligation of endosomal TLRs. |
| title_fullStr | The two-component adjuvant IC31® boosts type i interferon production of human monocyte-derived dendritic cells via ligation of endosomal TLRs. |
| title_full_unstemmed | The two-component adjuvant IC31® boosts type i interferon production of human monocyte-derived dendritic cells via ligation of endosomal TLRs. |
| title_short | The two-component adjuvant IC31® boosts type i interferon production of human monocyte-derived dendritic cells via ligation of endosomal TLRs. |
| title_sort | two component adjuvant ic31 r boosts type i interferon production of human monocyte derived dendritic cells via ligation of endosomal tlrs |
| url | http://europepmc.org/articles/PMC3566214?pdf=render |
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