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.