Lysosome-dependent activation of human dendritic cells by the vaccine adjuvant QS-21
Abstract: The adjuvant properties of the saponin QS-21 have been known for decades. It is a component of the Adjuvant System AS01 that is used in several vaccine candidates. QS-21 strongly potentiates both cellular and humoral immune responses to purified antigens, yet how it activates immune cells is largely unknown. Here, we report that QS-21 directly activated human monocyte-derived dendritic cells (moDCs) and promoted a pro-inflammatory transcriptional program. Cholesterol-dependent QS-21 endocytosis followed by lysosomal destabilization and Syk kinase activation were prerequisites for this response. Cathepsin B, a lysosomal cysteine protease, was essential for moDC activation in vitro and contributed to the adjuvant effects of QS-21 in vivo. Collectively, these findings provide new insights into the pathways involved in the direct activation of antigen-presenting cells by a clinically relevant QS-21 formulation
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Frontiers in immunology. - 7 (2017) , 663, ISSN: 1664-3224
- Klassifikation
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Medizin, Gesundheit
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2019
- Urheber
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Welsby, Iain
Detienne, Sophie
N’Kuli, Francisca
Thomas, Séverine
Wouters, Sandrine
Bechtold, Viviane
De Wit, Dominique
Gineste, Romain
Reinheckel, Thomas
Elouahabi, Abdelatif
Courtoy, Pierre J.
Didierlaurent, Arnaud M.
Goriely, Stanislas
- Beteiligte Personen und Organisationen
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Zentrum für Biochemie und Molekulare Zellforschung
- DOI
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10.3389/fimmu.2016.00663
- URN
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urn:nbn:de:bsz:25-freidok-1366711
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
14.08.2025, 11:01 MESZ
Datenpartner
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Beteiligte
- Welsby, Iain
- Detienne, Sophie
- N’Kuli, Francisca
- Thomas, Séverine
- Wouters, Sandrine
- Bechtold, Viviane
- De Wit, Dominique
- Gineste, Romain
- Reinheckel, Thomas
- Elouahabi, Abdelatif
- Courtoy, Pierre J.
- Didierlaurent, Arnaud M.
- Goriely, Stanislas
- Zentrum für Biochemie und Molekulare Zellforschung
- Universität
Entstanden
- 2019