Syndecan 4 Upregulation on Activated Langerhans Cells Counteracts Langerin Restriction to Facilitate Hepatitis C Virus Transmission.
Antigens, CD
/ genetics
Cell Differentiation
Cell Line
Coinfection
Disease Transmission, Infectious
HIV Infections
/ metabolism
HIV-1
/ physiology
Hepacivirus
/ physiology
Hepatitis C
/ metabolism
Homosexuality, Male
Humans
Langerhans Cells
/ physiology
Lectins, C-Type
/ genetics
Male
Mannose-Binding Lectins
/ genetics
RNA, Small Interfering
/ genetics
Sexually Transmitted Diseases
/ metabolism
Syndecan-4
/ genetics
Up-Regulation
heparan sulfate proteoglycans
heparan sulfates
hepatitis C virus
langerhans cells
langerin
syndecan 4
viral dissemination
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
17
09
2019
accepted:
05
03
2020
entrez:
16
4
2020
pubmed:
16
4
2020
medline:
30
3
2021
Statut:
epublish
Résumé
Sexually transmitted Hepatitis C virus (HCV) infections and high reinfections are a major concern amongst men who have sex with men (MSM) living with HIV-1 and HIV-negative MSM. Immune activation and/or HIV-1 coinfection enhance HCV susceptibility via sexual contact, suggesting that changes in immune cells or external factors are involved in increased susceptibility. Activation of anal mucosal Langerhans cells (LCs) has been implicated in increased HCV susceptibility as activated but not immature LCs efficiently retain and transmit HCV to other cells. However, the underlying molecular mechanism of transmission remains unclear. Here we identified the Heparan Sulfate Proteoglycan Syndecan 4 as the molecular switch, controlling HCV transmission by LCs. Syndecan 4 was highly upregulated upon activation of LCs and interference with Heparan Sulfate Proteoglycans or silencing of Syndecan 4 abrogated HCV transmission. These data strongly suggest that Syndecan 4 mediates HCV transmission by activated LCs. Notably, our data also identified the C-type lectin receptor langerin as a restriction factor for HCV infection and transmission. Langerin expression abrogated HCV infection in HCV permissive cells, whereas langerin expression on the Syndecan 4 expressing cell line strongly decreased HCV transmission to a target hepatoma cell line. These data suggest that the balanced interplay between langerin restriction and Syndecan 4 transmission determines HCV dissemination. Silencing of langerin enhanced HCV transmission whereas silencing Syndecan 4 on activated LCs decreased transmission. Blocking Heparan Sulfate Proteoglycans abrogated HCV transmission by LCs
Identifiants
pubmed: 32292405
doi: 10.3389/fimmu.2020.00503
pmc: PMC7118926
doi:
Substances chimiques
Antigens, CD
0
CD207 protein, human
0
Lectins, C-Type
0
Mannose-Binding Lectins
0
RNA, Small Interfering
0
Syndecan-4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
503Informations de copyright
Copyright © 2020 Nijmeijer, Eder, Langedijk, Kaptein, Meeussen, Zimmermann, Ribeiro and Geijtenbeek.
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