细胞内的天然免疫反应是抵抗外源病毒感染的第一道防线，其中I型与III型干扰素起着关键的作用。目前对于抗RNA病毒的免疫反应机制了解的比较深入，但对于肝脏抵抗DNA病毒感染的机制仍不清楚。此前研究发现，DNA病毒能够直接通过DNA或RNA中间物引起NF-KB的激活，但这一信号对于抗HBV免疫反应以及干扰素的产生是否具有联系仍不清楚。为了研究清楚上述问题，来自迈阿密大学医学院的Emmanuel Thomas课题组进行了深入的研究，相关结果发表在最近一期的《Journal of Immunology》杂志上。
Hepatitis B Virus and DNA Stimulation Trigger a Rapid Innate Immune Response through NF-κB
【Abstract】Cell-intrinsic innate immunity provides a rapid first line of defense to thwart invading viral pathogens through the production of antiviral and inflammatory genes. However, the presence of many of these signaling pathways in the liver and their role in hepatitis B virus (HBV) pathogenesis is unknown. Recent identification of intracellular DNA-sensing pathways and involvement in numerous diverse disease processes including viral pathogenesis and carcinogenesis suggest a role for these processes in HBV infection. To characterize HBV-intrinsic innate immune responses and the role of DNA- and RNA-sensing pathways in the liver, we used in vivo and in vitro models including analysis of gene expression in liver biopsies from HBV-infected patients. In addition, mRNA and protein expression were measured in HBV-stimulated and DNA-treated hepatoma cell lines and primary human hepatocytes. In this article, we report that HBV and foreign DNA stimulation results in innate immune responses characterized by the production of inflammatory chemokines in hepatocytes. Analysis of liver biopsies from HBV-infected patients supported a correlation among hepatic expression of specific chemokines. In addition, HBV elicits a much broader range of gene expression alterations. The induction of chemokines, including CXCL10, is mediated by melanoma differentiation–associated gene 5 and NF-κB–dependent pathways after HBV stimulation. In conclusion, HBV-stimulated pathways predominantly activate an inflammatory response that would promote the development of hepatitis. Understanding the mechanism underlying these virus–host interactions may provide new strategies to trigger noncytopathic clearance of covalently closed circular DNA to ultimately cure patients with HBV infection.