Binding of human papilloma virus L1 virus-like particles to dendritic cells is mediated through heparan sulfates and induces immune activation

Lot de Witte, Younes Zoughlami, Birgit Aengeneyndt, Guido David, Yvette van Kooyk, Lutz Gissmann, Teunis B H Geijtenbeek

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Immunization using human papilloma virus (HPV)-L1 virus-like particles (VLPs) induces a robust and effective immune response, which has recently resulted in the implementation of the HPV-L1 VLP vaccination in health programs. However, during infection, HPV can escape immune surveillance leading to latency and disease. Dendritic cells (DCs) induce effective immune responses after vaccination, but might also induce immune modulation during infection. The interaction of HPV-L1 VLPs with mucosal DCs determines the immune response. However, little is known about the receptors on mucosal DC subsets involved in HPV-L1 VLP binding. Therefore, we set out to investigate the interaction of HPV-L1 VLPs with the different mucosal DC subsets; the subepithelial DCs and Langerhans cells (LCs). We observed strong binding of HPV-L1 VLPs to both DCs and LCs. We did not observe an involvement for C-type lectins such as dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) and langerin. The HPV-L1 VLP binding to DCs was mediated through heparan sulfates, since it was abrogated by heparinase-II treatment. The heparan sulfate proteoglycan syndecan-3 binds VLPs and is expressed on both DCs and LCs. Binding of VLPs to DCs, but not to LCs, strongly correlated with the levels of heparan sulfates and syndecan-3, suggesting that syndecan-3 is the main receptor for HPV-L1 VLPs on DCs. VLP interaction with DCs resulted in the up-regulation of co-stimulatory molecules and the production of the cytokines IL-6, IL-8, IL-10 and IL-12p40. Our results support an important role for syndecan-3 as a HPV receptor on DCs, which could be important for both vaccine development and understanding HPV pathogenesis.

Original languageEnglish
Pages (from-to)679-91
Number of pages13
JournalImmunobiology
Volume212
Issue number9-10
DOIs
Publication statusPublished - 2007

Cite this

de Witte, Lot ; Zoughlami, Younes ; Aengeneyndt, Birgit ; David, Guido ; van Kooyk, Yvette ; Gissmann, Lutz ; Geijtenbeek, Teunis B H. / Binding of human papilloma virus L1 virus-like particles to dendritic cells is mediated through heparan sulfates and induces immune activation. In: Immunobiology. 2007 ; Vol. 212, No. 9-10. pp. 679-91.
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title = "Binding of human papilloma virus L1 virus-like particles to dendritic cells is mediated through heparan sulfates and induces immune activation",
abstract = "Immunization using human papilloma virus (HPV)-L1 virus-like particles (VLPs) induces a robust and effective immune response, which has recently resulted in the implementation of the HPV-L1 VLP vaccination in health programs. However, during infection, HPV can escape immune surveillance leading to latency and disease. Dendritic cells (DCs) induce effective immune responses after vaccination, but might also induce immune modulation during infection. The interaction of HPV-L1 VLPs with mucosal DCs determines the immune response. However, little is known about the receptors on mucosal DC subsets involved in HPV-L1 VLP binding. Therefore, we set out to investigate the interaction of HPV-L1 VLPs with the different mucosal DC subsets; the subepithelial DCs and Langerhans cells (LCs). We observed strong binding of HPV-L1 VLPs to both DCs and LCs. We did not observe an involvement for C-type lectins such as dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) and langerin. The HPV-L1 VLP binding to DCs was mediated through heparan sulfates, since it was abrogated by heparinase-II treatment. The heparan sulfate proteoglycan syndecan-3 binds VLPs and is expressed on both DCs and LCs. Binding of VLPs to DCs, but not to LCs, strongly correlated with the levels of heparan sulfates and syndecan-3, suggesting that syndecan-3 is the main receptor for HPV-L1 VLPs on DCs. VLP interaction with DCs resulted in the up-regulation of co-stimulatory molecules and the production of the cytokines IL-6, IL-8, IL-10 and IL-12p40. Our results support an important role for syndecan-3 as a HPV receptor on DCs, which could be important for both vaccine development and understanding HPV pathogenesis.",
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author = "{de Witte}, Lot and Younes Zoughlami and Birgit Aengeneyndt and Guido David and {van Kooyk}, Yvette and Lutz Gissmann and Geijtenbeek, {Teunis B H}",
year = "2007",
doi = "10.1016/j.imbio.2007.09.006",
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volume = "212",
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Binding of human papilloma virus L1 virus-like particles to dendritic cells is mediated through heparan sulfates and induces immune activation. / de Witte, Lot; Zoughlami, Younes; Aengeneyndt, Birgit; David, Guido; van Kooyk, Yvette; Gissmann, Lutz; Geijtenbeek, Teunis B H.

In: Immunobiology, Vol. 212, No. 9-10, 2007, p. 679-91.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Binding of human papilloma virus L1 virus-like particles to dendritic cells is mediated through heparan sulfates and induces immune activation

AU - de Witte, Lot

AU - Zoughlami, Younes

AU - Aengeneyndt, Birgit

AU - David, Guido

AU - van Kooyk, Yvette

AU - Gissmann, Lutz

AU - Geijtenbeek, Teunis B H

PY - 2007

Y1 - 2007

N2 - Immunization using human papilloma virus (HPV)-L1 virus-like particles (VLPs) induces a robust and effective immune response, which has recently resulted in the implementation of the HPV-L1 VLP vaccination in health programs. However, during infection, HPV can escape immune surveillance leading to latency and disease. Dendritic cells (DCs) induce effective immune responses after vaccination, but might also induce immune modulation during infection. The interaction of HPV-L1 VLPs with mucosal DCs determines the immune response. However, little is known about the receptors on mucosal DC subsets involved in HPV-L1 VLP binding. Therefore, we set out to investigate the interaction of HPV-L1 VLPs with the different mucosal DC subsets; the subepithelial DCs and Langerhans cells (LCs). We observed strong binding of HPV-L1 VLPs to both DCs and LCs. We did not observe an involvement for C-type lectins such as dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) and langerin. The HPV-L1 VLP binding to DCs was mediated through heparan sulfates, since it was abrogated by heparinase-II treatment. The heparan sulfate proteoglycan syndecan-3 binds VLPs and is expressed on both DCs and LCs. Binding of VLPs to DCs, but not to LCs, strongly correlated with the levels of heparan sulfates and syndecan-3, suggesting that syndecan-3 is the main receptor for HPV-L1 VLPs on DCs. VLP interaction with DCs resulted in the up-regulation of co-stimulatory molecules and the production of the cytokines IL-6, IL-8, IL-10 and IL-12p40. Our results support an important role for syndecan-3 as a HPV receptor on DCs, which could be important for both vaccine development and understanding HPV pathogenesis.

AB - Immunization using human papilloma virus (HPV)-L1 virus-like particles (VLPs) induces a robust and effective immune response, which has recently resulted in the implementation of the HPV-L1 VLP vaccination in health programs. However, during infection, HPV can escape immune surveillance leading to latency and disease. Dendritic cells (DCs) induce effective immune responses after vaccination, but might also induce immune modulation during infection. The interaction of HPV-L1 VLPs with mucosal DCs determines the immune response. However, little is known about the receptors on mucosal DC subsets involved in HPV-L1 VLP binding. Therefore, we set out to investigate the interaction of HPV-L1 VLPs with the different mucosal DC subsets; the subepithelial DCs and Langerhans cells (LCs). We observed strong binding of HPV-L1 VLPs to both DCs and LCs. We did not observe an involvement for C-type lectins such as dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) and langerin. The HPV-L1 VLP binding to DCs was mediated through heparan sulfates, since it was abrogated by heparinase-II treatment. The heparan sulfate proteoglycan syndecan-3 binds VLPs and is expressed on both DCs and LCs. Binding of VLPs to DCs, but not to LCs, strongly correlated with the levels of heparan sulfates and syndecan-3, suggesting that syndecan-3 is the main receptor for HPV-L1 VLPs on DCs. VLP interaction with DCs resulted in the up-regulation of co-stimulatory molecules and the production of the cytokines IL-6, IL-8, IL-10 and IL-12p40. Our results support an important role for syndecan-3 as a HPV receptor on DCs, which could be important for both vaccine development and understanding HPV pathogenesis.

KW - Capsid Proteins/immunology

KW - Cell Adhesion Molecules/metabolism

KW - Cells, Cultured

KW - Cytokines/immunology

KW - Dendritic Cells/cytology

KW - Heparitin Sulfate/metabolism

KW - Human papillomavirus 16/immunology

KW - Humans

KW - Langerhans Cells/cytology

KW - Lectins, C-Type/metabolism

KW - Oncogene Proteins, Viral/immunology

KW - Papillomavirus Vaccines/immunology

KW - Polysaccharide-Lyases/metabolism

KW - Receptors, Cell Surface/metabolism

KW - Syndecan-3/metabolism

KW - Up-Regulation

U2 - 10.1016/j.imbio.2007.09.006

DO - 10.1016/j.imbio.2007.09.006

M3 - Article

VL - 212

SP - 679

EP - 691

JO - Immunobiology

JF - Immunobiology

SN - 0171-2985

IS - 9-10

ER -