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Published on: September 25, 2019
Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells
Isabelle E Vincent1, Claudia Zannetti, Julie Lucifora
1INSERM, U871, Lyon, France. isabelle.vincent@inserm.fr
Hepatitis B virus (HBV) impairs plasmacytoid dendritic cell (pDC) function by blocking Toll-Like Receptor 9 (TLR9) signaling, hindering type I interferon production. This immune evasion aids chronic HBV infection persistence.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Plasmacytoid dendritic cells (pDCs) are crucial for antiviral immunity, producing type I interferons (IFNs) via Toll-Like Receptor (TLR) signaling.
- Hepatitis B virus (HBV) infection is associated with impaired pDC function and reduced IFN-α production.
Purpose of the Study:
- To investigate the mechanisms by which HBV interferes with TLR9-mediated IFN-α production by pDCs.
- To identify viral strategies that contribute to immune evasion in chronic HBV infection.
Main Methods:
- Ex vivo stimulation of pDCs with TLR9 ligands.
- Analysis of TLR9 expression, signaling pathways (MyD88-IRAK4), and IRF7 activation.
- Detection of CpG motifs in HBV DNA.
- Assessment of TLR9 expression in peripheral blood mononuclear cells (PBMCs) from HBV patients.
Main Results:
- HBV particle internalization inhibits TLR9- but not TLR7-mediated IFN-α secretion.
- HBV down-regulates TLR9 transcription and protein levels in pDCs and B cells.
- HBV interferes with the MyD88-IRAK4 axis and IRF7 activation.
- HBV DNA contains CpG motifs that suppress TLR9 activation.
- TLR9 is downregulated in PBMCs from patients with chronic hepatitis and hepatocellular carcinoma.
Conclusions:
- HBV employs multiple strategies to evade TLR9-mediated immune responses in pDCs and B cells.
- These immune escape mechanisms likely contribute to the establishment and persistence of chronic HBV infection.
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