par Welsby, Iain 
;Detienne, Sophie ;N'Kuli, Francisca;Thomas, Séverine ;Wouters, Sandrine ;Bechtold, Viviane;De Wit, Dominique ;Gineste, Romain;Reinheckel, Thomas;Elouahabi, Abdelatif ;Courtoy, P.;Didierlaurent, Arnaud M;Goriely, Stanislas
Référence Frontiers in immunology, 7, page (663)
Publication Publié, 2016
;Detienne, Sophie ;N'Kuli, Francisca;Thomas, Séverine ;Wouters, Sandrine ;Bechtold, Viviane;De Wit, Dominique ;Gineste, Romain;Reinheckel, Thomas;Elouahabi, Abdelatif ;Courtoy, P.;Didierlaurent, Arnaud M;Goriely, Stanislas Référence Frontiers in immunology, 7, page (663)
Publication Publié, 2016
Article révisé par les pairs
| Résumé : | 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. |
