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Tumor necrosis factor: The key to hepatitis B viral clearance

Cellular & Molecular Immunology volume 15, pages 731–733 (2018)Cite this article

The immunopathogenesis of hepatitis B virus (HBV) involves a complex interaction of innate and adaptive immune response associated with several cytokines. However, due to experimental limitations, very limited and even no activation of the innate immune response can be demonstrated in acute HBV infection. The role of innate immunity and the key innate effectors for HBV clearance is still uncertain. It is also not clear whether clinical use of TNF inhibitors in treating rheumatoid arthritis and other autoimmune disease patients with chronic HBV infection would affect viral reactivation. However, in a recent paper in Cell Mol Immunol, Chyuan et al. reported that under TNF-α blockade, HBV viral clearance was impaired with persistent elevated HBV viral load in a dose and temporal-dependent manner.1 It demonstrates that a deficiency of TNF-α reduces viral clearance and promotes HBV persistence in a mouse model, and the impairment of HBV clearance under anti-TNF-α occurs at an early time point of HBV infection, suggesting that HBV may reactivate during therapy with TNF inhibitors. The results together with previous reports support that TNF is a key innate cytokine required to clear HBV.2,3 It also provides evidence that therapy with TNF inhibitors may impair immune response to HBV clearance.

Weak or even absent activation of innate immunity seems to be the hallmark of acute HBV infection. Moreover, pro-inflammatory cytokines are often undetectable during the early phases of HBV infection. For over two decades, numerous efforts have been reported in search for critical innate effectors in HBV clearance. It is suggested that an efficient control of HBV infection requires the coordinated actions of innate immune cells and viral specific T cells; however, the innate immunity and key cytokine related to HBV clearance are still not well defined. Acute HBV infection models of both woodchucks and chimpanzees also fails to verify the role of innate immune response in HBV infection. It is an overall scenario of weak or even transcription silence in activation of innate immunity to HBV, in particular, the type I interferon (IFN-I) response. Apparent lack of the IFN-I response is observed in HBV infection and thereby considered as one of the underlying mechanisms for HBV to escape innate recognition.4,5 Different lines of evidence indicate that it is questionable if HBV can actually be sensed by the innate immunity.6 In fact, the mechanisms how innate immune system senses HBV are still not elucidated and it is also unclear which HBV molecules (DNA, RNA or viral proteins) are actually recognized by the pattern recognition receptors (PRR) and thereby trigger the antiviral response.

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Acknowledgements

This work was financially supported by a grant from the Ministry of Science and Technology (MOST), Taiwan

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Authors and Affiliations

  1. Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan, China

    I-Tsu Chyuan

  2. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, China

    I-Tsu Chyuan

  3. Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, China

    Ping-Ning Hsu

  4. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, China

    Ping-Ning Hsu

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Correspondence to Ping-Ning Hsu.

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Chyuan, IT., Hsu, PN. Tumor necrosis factor: The key to hepatitis B viral clearance. Cell Mol Immunol 15, 731–733 (2018). https://doi.org/10.1038/cmi.2017.139

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