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dc.contributor.authorKooijman, Sietske
dc.contributor.authorBrummelman, Jolanda
dc.contributor.authorvan Els, Cécile A C M
dc.contributor.authorMarino, Fabio
dc.contributor.authorHeck, Albert J R
dc.contributor.authorMommen, Geert P M
dc.contributor.authorMetz, Bernard
dc.contributor.authorKersten, Gideon F A
dc.contributor.authorPennings, Jeroen L A
dc.contributor.authorMeiring, Hugo D
dc.date.accessioned2018-01-16T09:32:43Z
dc.date.available2018-01-16T09:32:43Z
dc.date.issued2018-01-06
dc.identifier.citationNovel identified aluminum hydroxide-induced pathways proof monocyte activation and pro-inflammatory preparedness. 2018 J Proteomicsen
dc.identifier.issn1876-7737
dc.identifier.pmid29317357
dc.identifier.doi10.1016/j.jprot.2017.12.021
dc.identifier.urihttp://hdl.handle.net/10029/621164
dc.description.abstractAluminum-based adjuvants are the most widely used adjuvants in human vaccines. A comprehensive understanding of the mechanism of action of aluminum adjuvants at the molecular level, however, is still elusive. Here, we unravel the effects of aluminum hydroxide Al(OH)3 by a systems-wide analysis of the Al(OH)3-induced monocyte response. Cell response analysis by cytokine release was combined with (targeted) transcriptome and full proteome analysis. Results from this comprehensive study revealed two novel pathways to become activated upon monocyte stimulation with Al(OH)3: the first pathway was IFNβ signaling possibly induced by DAMP sensing pathways like TLR or NOD1 activation, and second the HLA class I antigen processing and presentation pathway. Furthermore, known mechanisms of the adjuvant activity of Al(OH)3 were elucidated in more detail such as inflammasome and complement activation, homeostasis and HLA-class II upregulation, possibly related to increased IFNγ gene expression. Altogether, our study revealed which immunological pathways are activated upon stimulation of monocytes with Al(OH)3, refining our knowledge on the adjuvant effect of Al(OH)3 in primary monocytes.
dc.language.isoenen
dc.rightsArchived with thanks to Journal of proteomicsen
dc.titleNovel identified aluminum hydroxide-induced pathways proof monocyte activation and pro-inflammatory preparedness.en
dc.typeArticleen
dc.identifier.journalJ Proteomics 2018; 175:144-55en
html.description.abstractAluminum-based adjuvants are the most widely used adjuvants in human vaccines. A comprehensive understanding of the mechanism of action of aluminum adjuvants at the molecular level, however, is still elusive. Here, we unravel the effects of aluminum hydroxide Al(OH)3 by a systems-wide analysis of the Al(OH)3-induced monocyte response. Cell response analysis by cytokine release was combined with (targeted) transcriptome and full proteome analysis. Results from this comprehensive study revealed two novel pathways to become activated upon monocyte stimulation with Al(OH)3: the first pathway was IFNβ signaling possibly induced by DAMP sensing pathways like TLR or NOD1 activation, and second the HLA class I antigen processing and presentation pathway. Furthermore, known mechanisms of the adjuvant activity of Al(OH)3 were elucidated in more detail such as inflammasome and complement activation, homeostasis and HLA-class II upregulation, possibly related to increased IFNγ gene expression. Altogether, our study revealed which immunological pathways are activated upon stimulation of monocytes with Al(OH)3, refining our knowledge on the adjuvant effect of Al(OH)3 in primary monocytes.


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