Potential conflict of interest: Nothing to report.
Pathogen DNA also contributes to interferon regulatory factor 3 activation in hepatic cells: Implications for alcoholic liver diseases†
Article first published online: 17 DEC 2010
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 53, Issue 5, pages 1783–1784, May 2011
How to Cite
Wang, Y., Guo, Y., Wang, F. and Sun, S. (2011), Pathogen DNA also contributes to interferon regulatory factor 3 activation in hepatic cells: Implications for alcoholic liver diseases. Hepatology, 53: 1783–1784. doi: 10.1002/hep.24089
- Issue published online: 22 APR 2011
- Article first published online: 17 DEC 2010
- Accepted manuscript online: 24 NOV 2010 11:58AM EST
To the Editor:
We read with great interest the recent article by Petrasek and colleagues,1 who reported that interferon regulatory factor 3 (IRF3) activation and type I interferon (IFN) production in parenchymal cells have protective effects in patients with alcoholic liver disease (ALD). The authors also suggested that IRF3 activation is a result of hepatic exposure to bacterial lipopolysaccharide (LPS). However, the authors failed to discuss gut bacterial and hepatic virus DNA, which is another immune-stimulating agent in addition to LPS that may also contribute to IRF3 activation in liver parenchymal cells and should be involved in the process of ALD.
Besides LPS, excessive drinking of alcohol also results in an elevation of bacterial DNA in the portal blood.2 Recent studies have indicated that intracellular bacterial DNA can strongly activate IRF3 in liver parenchymal cells3 and thus induce the production of type I IFNs. In this respect, we suggest that gut-derived bacterial DNA also contributes to IRF3 activation and may play a key role in the prevention of alcoholic liver injury.
We also believe that DNA-mediated hepatic IRF3 activation has great significance in China because of the high rate of hepatitis B virus (HBV) infection. Intracellular virus DNA4 has been proved to strongly activate IRF3 and induce type I IFN production. However, recent studies have found that components of HBV3 inhibit IRF3 activation via cleavage of the mitochondrial antiviral signaling protein, which is an essential component that activates IRF3 and thus induces the production of type I IFNs.5 Considering the current findings by Petrasek et al.,1 we hypothesize that HBV may also hinder the prevention functions of IRF3 and type I IFNs via the inhibition of the mitochondrial antiviral signaling protein and that HBV infection may increase the risk of ALD. This requires further investigation.
- 1Interferon regulatory factor 3 and type I interferons are protective in alcoholic liver injury in mice via cross-talk of parenchymal and myeloid cells. Hepatology 2011; DOI: 10.1002/hep.24059., , , , , , et al.
- 2Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1beta in mice. Gastroenterology 2011; 139: 323-334., , , , , , et al.
- 3The hepatitis B virus X protein disrupts innate immunity by downregulating mitochondrial antiviral signaling protein. J Immunol 2011; 185: 1158-1168., , , , , , et al.
- 4RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell 2009; 138: 576-591., , .
- 5The specific and essential role of MAVS in antiviral innate immune responses. Immunity 2006; 24: 633-642., , , , , , et al.
Yue Wang M.D.*, Yingjun Guo M.D.*, Fang Wang M.D.*, Shuhan Sun M.D.*, * Department of Medical Genetics, Second Military Medical University, Shanghai, People's Republic of China.