The L1 major capsid protein of HPV16 differentially modulates APC trafficking according to the vaccination or natural infection context.
Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The progression of cervical lesions suggests that viral antigens are not adequately presented to the immune system. The aim of this study was to determine whether HPV16 viral particles can influence the trafficking of human DC/Langerhans cells (LC), either by direct interactions with DC or following incubation with human normal keratinocytes that are in close contact with LC in the squamous epithelium. We first demonstrated that HPV16 L1 major capsid protein, when self-assembled into virus-like particles (VLP), is able to induce in DC an over-expression of CXC receptor 4 (CXCR4) via the activation of the NF-κB signaling pathway and to enhance DC motility in the presence of CXCL12, suggesting an ability to migrate towards lymph nodes. We also showed that conditioned media of HPV16 VLP-treated keratinocytes induce a lower LC migration than those from untreated keratinocytes and that prostaglandin E2 (PGE(2)), detected in HPV16 VLP-treated keratinocyte supernatants, may reduce LC recruitment into the squamous epithelium. Taken together, our data demonstrate that HPV16 VLP may differentially regulate the immune protective response according to their target cells.
Department of Experimental Pathology, University Hospital of Liège, CHU Sart Tilman, Liège, Belgium.
Ludivine
L
Herman
Pascale
P
Hubert
Michaël
M
Herfs
Gaelle
G
Kustermans
Yves
Y
Henrotin
Latifa
L
Bousarghin
Jacques
J
Boniver
Philippe
P
Delvenne
D036022:Capsid Proteins / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D052162:Human papillomavirus 16 / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology / Q000821:virology; D007801:Langerhans Cells / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000276:immunology
C527276:CXCR4 protein, human; D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D019718:Receptors, CXCR4; C063317:L1 protein, Human papillomavirus type 16; D015232:Dinoprostone