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Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

Cellular & Molecular Immunology volume 12, pages 273–282 (2015)Cite this article

Abstract

It is well accepted that adaptive immunity plays a key role in the control of hepatitis B virus (HBV) infection. In contrast, the contribution of innate immunity has only received attention in recent years. Toll-like receptors (TLRs) sense pathogen-associated molecule patterns and activate antiviral mechanisms, including intracellular antiviral pathways and the production of antiviral effector interferons (IFNs) and pro-inflammatory cytokines. Experimental results from in vitro and in vivo models have demonstrated that TLRs mediate the activation of cellular signaling pathways and the production of antiviral cytokines, resulting in a suppression of HBV replication. However, HBV infection is associated with downregulation of TLR expression on host cells and blockade of the activation of downstream signaling pathways. In primary HBV infection, TLRs may slow down HBV infection, but contribute only indirectly to viral clearance. Importantly, TLRs may modulate HBV-specific T- and B-cell responses in vivo, which are essential for the termination of HBV infection. Thus, TLR agonists are promising candidates to act as immunomodulators for the treatment of chronic HBV infection. Antiviral treatment may recover TLR expression and function in chronic HBV infection and may increase the efficacy of therapeutic approaches based on TLR activation. A combined therapeutic strategy with antiviral treatment and TLR activation could facilitate the restoration of HBV-specific immune responses and thereby, achieve viral clearance in chronically infected HBV patients.

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Acknowledgements

This work was supported by grants from Deutsche Forschungsgemeinschaft TRR60, GK1045 and RTG 1949.

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  1. Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    Zhiyong Ma & Mengji Lu

  2. Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China

    Zhiyong Ma

  3. Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China

    Ejuan Zhang

  4. Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Dongliang Yang

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Ma, Z., Zhang, E., Yang, D. et al. Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses. Cell Mol Immunol 12, 273–282 (2015). https://doi.org/10.1038/cmi.2014.112

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