Polymorphonuclear neutrophil-derived ectosomes interfere with the maturation of monocyte-derived dendritic cells.
Polymorphonuclear neutrophils (PMNs) are a key component of the innate immune system. Their activation leads to the release of potent antimicrobial agents through degranulation. Simultaneously, PMNs release cell surface-derived microvesicles, so-called ectosomes (PMN-Ect). PMN-Ect are rightside-out vesicles with a diameter of 50-200 nm. They expose phosphatidylserine in the outer leaflet of their membrane and down-modulate monocyte/macrophage-activation in vitro. In this study, we analyzed the effects of PMN-Ect on maturation of human monocyte-derived dendritic cells (MoDCs). Intriguingly, exposing immature MoDCs to PMN-Ect modified their morphology, reduced their phagocytic activity, and increased the release of TGF-beta1. When immature MoDCs were incubated with PMN-Ect and stimulated with the TLR4 ligand LPS, the maturation process was partially inhibited as evidenced by reduced expression of cell surface markers (CD40, CD80, CD83, CD86, and HLA-DP DQ DR), inhibition of cytokine-release (IL-8, IL-10, IL-12, and TNF-alpha), and a reduced capacity to induce T cell proliferation. Together these data provide evidence that PMN-Ect have the ability to modify MoDC maturation and function. PMN-Ect may thus represent an as yet unidentified host-factor influencing MoDC maturation at the site of injury, thereby possibly impacting on downstream MoDC-dependent immunity.
Eken
Ceylan
C
Department of Research, Immunonephrology Laboratory, University Hospital Basel, Switzerland. ceylan.eken@unibas.ch
Gasser
Olivier
O
Zenhaeusern
Gabriela
G
Oehri
Ineke
I
Hess
Christoph
C
Schifferli
Jürg A
JA
D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D004705:Endocytosis; D006801:Humans; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000954:Antigens, Surface; D016207:Cytokines