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Hepatitis B Virus Impairs TLR9 Expression and Function in Plasmacytoid Dendritic Cells

Abstract : 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-a following ex vivo stimulation with TLR9 ligands. Here we highlight several strategies used by HBV to block IFN-a 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-a 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-a 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.
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https://hal.archives-ouvertes.fr/hal-03313302
Contributor : Julie Lucifora <>
Submitted on : Tuesday, August 3, 2021 - 5:19:09 PM
Last modification on : Wednesday, August 4, 2021 - 11:04:55 AM

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Article 9 - 2011 - Vincent, Pl...
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Isabelle Vincent, Claudia Zannetti, Julie Lucifora, Helene Norder, Ulrike Protzer, et al.. Hepatitis B Virus Impairs TLR9 Expression and Function in Plasmacytoid Dendritic Cells. PLoS ONE, Public Library of Science, 2011, 6 (10), pp.e26315. ⟨10.1371/journal.pone.0026315⟩. ⟨hal-03313302⟩

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