Tumor necrosis factor: The key to hepatitis B viral clearance
I-Tsu Chyuan & Ping-Ning Hsu
Cellular and Molecular Immunology | Download Citation
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.作者: StephenW 时间: 2018-9-25 20:39
"So far, with the lack of type I IFN response, the TNF pathway is the only innate response demonstrated to play a key role in HBV clearance. Nevertheless, it is necessary to clarify how innate immune cells are triggered and regulated to produce TNF-α during HBV infection. As one possible mechanism that we have previously reported, HBV core protein is sensed by the innate immune system to induce TNF-α production and thereby viral clearance; which can also be abolished by TNF-α blockade.2"
“到目前为止，由于缺乏I型IFN反应，TNF途径是唯一在HBV清除中发挥关键作用的先天反应。然而，有必要澄清先天免疫细胞如何被触发和调节以产生TNF- HBV感染期间的α。作为我们之前报道的一种可能的机制，HBV核心蛋白被先天免疫系统感知，诱导TNF-α的产生，从而导致病毒清除;也可以通过TNF-α阻断来消除。