Human papillomavirus 16 virus-like particles use heparan sulfates to bind dendritic cells and colocalize with langerin in Langerhans cells.
Langerhans cells (LC), the immature dendritic cells (DC) that reside in epithelial tissues are among the first immune cells to encounter human papillomavirus (HPV) and are not activated by HPV virus-like particles (VLPs) in contrast to DC. The notion that the differences in response to HPV VLPs between LC and DC are associated with different types of cell binding and intracellular trafficking has been addressed. Inhibition experiments with heparin and sodium chlorate showed that heparan sulfates are necessary for HPV 16 VLPs to bind to DC but not to LC. Electron microscopy analysis demonstrated a colocalization of HPV 16 VLPs and langerin, which is expressed only by LC. This colocalization was observed on the cell surface but also in cytoplasmic vesicles. As anti-langerin antibodies, HPV 16 VLPs were associated with a faster entry kinetics in LC, as reflected by the fact that VLPs were observed near the nuclear membrane of LC within 10 min whereas more than 60 min were needed in DC. However, no difference between LC and DC was observed for the endocytosis pathway. HPV 16 VLPs entered in both DC and LC by a clathrin-dependent-pathway and were then localized in large cytoplasmic vesicles resembling endosomes.
Bousarghin
Latifa
L
University Hospital of Liège, Department of Pathology, Tour de Pathologie B35, B-4000 Liège, Belgium.
Hubert
Pascale
P
University Hospital of Liège, Department of Pathology, Tour de Pathologie B35, B-4000 Liège, Belgium.
Franzen
Elisabeth
E
University Hospital of Liège, Department of Pathology, Tour de Pathologie B35, B-4000 Liège, Belgium.
Jacobs
Nathalie
N
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.|University Hospital of Liège, Department of Pathology, Tour de Pathologie B35, B-4000 Liège, Belgium.
Boniver
Jacques
J
University Hospital of Liège, Department of Pathology, Tour de Pathologie B35, B-4000 Liège, Belgium.
Delvenne
Philippe
P
University Hospital of Liège, Department of Pathology, Tour de Pathologie B35, B-4000 Liège, Belgium.
D015703:Antigens, CD; D000954:Antigens, Surface / Q000378:metabolism*; D002462:Cell Membrane / Q000648:ultrastructure / Q000821:virology; D022162:Cytoplasmic Vesicles / Q000648:ultrastructure / Q000821:virology; D003713:Dendritic Cells / Q000821:virology*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D007801:Langerhans Cells / Q000821:virology*; D037181:Lectins, C-Type / Q000378:metabolism*; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D008854:Microscopy, Electron; D027383:Papillomaviridae / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology; D022701:Virosomes / Q000378:metabolism*
D015703:Antigens, CD; D000954:Antigens, Surface; D006497:Heparan Sulfate; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D011991:Receptors, Virus; D022701:Virosomes; C121916:CD207 protein, human