Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) play a key role in detecting pathogens by producing large amounts of type I interferon (IFN) by sensing the presence of viral infections through the Toll-Like Receptor (TLR) pathway. TLR9 is a sensor of viral and bacterial DNA motifs and activates the IRF7 transcr...

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Autores principales:	Isabelle E Vincent, Claudia Zannetti, Julie Lucifora, Helene Norder, Ulrike Protzer, Pierre Hainaut, Fabien Zoulim, Massimo Tommasino, Christian Trépo, Uzma Hasan, Isabelle Chemin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d45d4ebe64094904980916be6ddcd6cc
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spelling	oai:doaj.org-article:d45d4ebe64094904980916be6ddcd6cc2021-11-18T07:35:48ZHepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells.1932-620310.1371/journal.pone.0026315https://doaj.org/article/d45d4ebe64094904980916be6ddcd6cc2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22046272/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Plasmacytoid dendritic cells (pDCs) play a key role in detecting pathogens by producing large amounts of type I interferon (IFN) by sensing the presence of viral infections through the Toll-Like Receptor (TLR) pathway. TLR9 is a sensor of viral and bacterial DNA motifs and activates the IRF7 transcription factor which leads to type I IFN secretion by pDCs. However, during chronic hepatitis B virus (HBV) infection, pDCs display an impaired ability to secrete IFN-α following ex vivo stimulation with TLR9 ligands. Here we highlight several strategies used by HBV to block IFN-α production through a specific impairment of the TLR9 signaling. Our results show that HBV particle internalisation could inhibit TLR9- but not TLR7-mediated secretion of IFN-α by pDCs. We observed that HBV down-regulated TLR9 transcriptional activity in pDCs and B cells in which TLR9 mRNA and protein levels were reduced. HBV can interfere with TLR9 activity by blocking the MyD88-IRAK4 axis and Sendai virus targeting IRF7 to block IFN-α production. Neutralising CpG motif sequences were identified within HBV DNA genome of genotypes A to H which displayed a suppressive effect on TLR9-immune activation. Moreover, TLR9 mRNA and protein were downregulated in PBMCs from patients with HBV-associated chronic hepatitis and hepatocellular carcinoma. Thus HBV has developed several escape mechanisms to avoid TLR9 activation in both pDCs and B lymphocytes, which may in turn contribute to the establishment and/or persistence of chronic infection.Isabelle E VincentClaudia ZannettiJulie LuciforaHelene NorderUlrike ProtzerPierre HainautFabien ZoulimMassimo TommasinoChristian TrépoUzma HasanIsabelle CheminPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e26315 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Isabelle E Vincent Claudia Zannetti Julie Lucifora Helene Norder Ulrike Protzer Pierre Hainaut Fabien Zoulim Massimo Tommasino Christian Trépo Uzma Hasan Isabelle Chemin Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells.
description	Plasmacytoid dendritic cells (pDCs) play a key role in detecting pathogens by producing large amounts of type I interferon (IFN) by sensing the presence of viral infections through the Toll-Like Receptor (TLR) pathway. TLR9 is a sensor of viral and bacterial DNA motifs and activates the IRF7 transcription factor which leads to type I IFN secretion by pDCs. However, during chronic hepatitis B virus (HBV) infection, pDCs display an impaired ability to secrete IFN-α following ex vivo stimulation with TLR9 ligands. Here we highlight several strategies used by HBV to block IFN-α production through a specific impairment of the TLR9 signaling. Our results show that HBV particle internalisation could inhibit TLR9- but not TLR7-mediated secretion of IFN-α by pDCs. We observed that HBV down-regulated TLR9 transcriptional activity in pDCs and B cells in which TLR9 mRNA and protein levels were reduced. HBV can interfere with TLR9 activity by blocking the MyD88-IRAK4 axis and Sendai virus targeting IRF7 to block IFN-α production. Neutralising CpG motif sequences were identified within HBV DNA genome of genotypes A to H which displayed a suppressive effect on TLR9-immune activation. Moreover, TLR9 mRNA and protein were downregulated in PBMCs from patients with HBV-associated chronic hepatitis and hepatocellular carcinoma. Thus HBV has developed several escape mechanisms to avoid TLR9 activation in both pDCs and B lymphocytes, which may in turn contribute to the establishment and/or persistence of chronic infection.
format	article
author	Isabelle E Vincent Claudia Zannetti Julie Lucifora Helene Norder Ulrike Protzer Pierre Hainaut Fabien Zoulim Massimo Tommasino Christian Trépo Uzma Hasan Isabelle Chemin
author_facet	Isabelle E Vincent Claudia Zannetti Julie Lucifora Helene Norder Ulrike Protzer Pierre Hainaut Fabien Zoulim Massimo Tommasino Christian Trépo Uzma Hasan Isabelle Chemin
author_sort	Isabelle E Vincent
title	Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells.
title_short	Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells.
title_full	Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells.
title_fullStr	Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells.
title_full_unstemmed	Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells.
title_sort	hepatitis b virus impairs tlr9 expression and function in plasmacytoid dendritic cells.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/d45d4ebe64094904980916be6ddcd6cc
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Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells.

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