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

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
Frontiers in immunology. - 7 (2017) , 663, ISSN: 1664-3224

Classification
Medizin, Gesundheit

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2019
Creator
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
Contributor
Zentrum für Biochemie und Molekulare Zellforschung

DOI
10.3389/fimmu.2016.00663
URN
urn:nbn:de:bsz:25-freidok-1366711
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 11:01 AM CEST

Data provider

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Associated

  • 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

Time of origin

  • 2019

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