Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201951/ https://www.ncbi.nlm.nih.gov/pubmed/22046272 http://dx.doi.org/10.1371/journal.pone.0026315 |
_version_ | 1782214955729158144 |
---|---|
author | Vincent, Isabelle E. Zannetti, Claudia Lucifora, Julie Norder, Helene Protzer, Ulrike Hainaut, Pierre Zoulim, Fabien Tommasino, Massimo Trépo, Christian Hasan, Uzma Chemin, Isabelle |
author_facet | Vincent, Isabelle E. Zannetti, Claudia Lucifora, Julie Norder, Helene Protzer, Ulrike Hainaut, Pierre Zoulim, Fabien Tommasino, Massimo Trépo, Christian Hasan, Uzma Chemin, Isabelle |
author_sort | Vincent, Isabelle E. |
collection | PubMed |
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 | Online Article Text |
id | pubmed-3201951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32019512011-11-01 Hepatitis B Virus Impairs TLR9 Expression and Function in Plasmacytoid Dendritic Cells Vincent, Isabelle E. Zannetti, Claudia Lucifora, Julie Norder, Helene Protzer, Ulrike Hainaut, Pierre Zoulim, Fabien Tommasino, Massimo Trépo, Christian Hasan, Uzma Chemin, Isabelle PLoS One Research Article 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. Public Library of Science 2011-10-25 /pmc/articles/PMC3201951/ /pubmed/22046272 http://dx.doi.org/10.1371/journal.pone.0026315 Text en Vincent et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Vincent, Isabelle E. Zannetti, Claudia Lucifora, Julie Norder, Helene Protzer, Ulrike Hainaut, Pierre Zoulim, Fabien Tommasino, Massimo Trépo, Christian Hasan, Uzma Chemin, Isabelle Hepatitis B Virus Impairs TLR9 Expression and Function in Plasmacytoid Dendritic Cells |
title | 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_short | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201951/ https://www.ncbi.nlm.nih.gov/pubmed/22046272 http://dx.doi.org/10.1371/journal.pone.0026315 |
work_keys_str_mv | AT vincentisabellee hepatitisbvirusimpairstlr9expressionandfunctioninplasmacytoiddendriticcells AT zannetticlaudia hepatitisbvirusimpairstlr9expressionandfunctioninplasmacytoiddendriticcells AT luciforajulie hepatitisbvirusimpairstlr9expressionandfunctioninplasmacytoiddendriticcells AT norderhelene hepatitisbvirusimpairstlr9expressionandfunctioninplasmacytoiddendriticcells AT protzerulrike hepatitisbvirusimpairstlr9expressionandfunctioninplasmacytoiddendriticcells AT hainautpierre hepatitisbvirusimpairstlr9expressionandfunctioninplasmacytoiddendriticcells AT zoulimfabien hepatitisbvirusimpairstlr9expressionandfunctioninplasmacytoiddendriticcells AT tommasinomassimo hepatitisbvirusimpairstlr9expressionandfunctioninplasmacytoiddendriticcells AT trepochristian hepatitisbvirusimpairstlr9expressionandfunctioninplasmacytoiddendriticcells AT hasanuzma hepatitisbvirusimpairstlr9expressionandfunctioninplasmacytoiddendriticcells AT cheminisabelle hepatitisbvirusimpairstlr9expressionandfunctioninplasmacytoiddendriticcells |