Abstract
BackgroundHepatitis B virus (HBV) is a hepatotropic DNA virus, and its DNA may be a potent inflammatory molecule. Interferon-inducible protein 16 (IFI16), a newly discovered DNA sensor, plays an important role in the process of inflammation in viral infections. Our study sought to identify a correlation between IFI16 expression and inflammation in patients with chronic hepatitis B (CHB) and HBV-associated acute-on-chronic liver failure (HBV-ACLF).MethodsWe performed flow cytometry to measure IFI16 levels in peripheral blood mononuclear cells (PBMC) and used immunohistochemistry and western blotting to measure IFI16 protein levels in liver tissues. The cellular source of IFI16 was detected using double immunofluorescence. All datum were analyzed using SPSS 13.0 and GraphPad Prism 6.ResultsThe number of IFI16+ cells was significantly associated with the degree of inflammation. In detail, the number of IFI16+ cells was higher in livers but lower in PBMCs in HBV-ACLF patients than those in CHB patients and healthy controls. There was no significant difference between CHB patients and healthy controls in numbers of IFI6+ cells in livers and PBMCs. There was no significant relationship between IFI16 expression levels and HBV parameters. Furthermore, IFI16 was expressed in the nucleus of Kupffer cells (KCs), endothelial cells, natural killer cells, dendritic cells, and hepatic stellate cells in healthy donors and CHB patients, but only in the cytoplasm of KCs in the livers of HBV-ACLF patients.ConclusionsIFI16 was closely related to the degree of inflammation in CHB and HBV-ACLF patients and may serve as a vital contributor to the pathogeneses of liver damage in HBV-ACLF.
Highlights
Hepatitis B virus (HBV) is a hepatotropic DNA virus, and its DNA may be a potent inflammatory molecule
Our laboratory investigated whether Interferon-inducible protein 16 (IFI16) is expressed in peripheral blood mononuclear cells (PBMCs) and livers in chronic hepatitis B (CHB) and HBVACLF patients and whether HBV DNA is recognized by IFI16.In addition, we examined the correlation between IFI16 expression and the inflammation
Expression of IFI16 in PBMCs of HBV patients and healthy controls We first examined the expression of IFI16 in PBMCs from 31 patients with CHB,13 patients with ACLF, and 16 healthy controls using flow cytometry
Summary
Hepatitis B virus (HBV) is a hepatotropic DNA virus, and its DNA may be a potent inflammatory molecule. Interferon-inducible protein 16 (IFI16), a newly discovered DNA sensor, plays an important role in the process of inflammation in viral infections. Interferon inducible protein 16 (IFI16), a newly discovered molecule that senses DNA in cells and stimulates stimulator of IFN genes (STING)-dependent IFN expression. Previous studies showed that AIM2 can stimulate inflammasome activation and downstream cleavage of pro-interleukin (IL)1b and proIL18 to bioactive cytokines via interactions between the PYD and the inflammasome adaptor protein ASC [4]. Such AIM2-ASC inflammatory signaling pathways activation may occur during HBV infection [5]. Studies have demonstrated the induction of IFN responses during infection with herpes simplex virus (HSV), Human cytomegalovirus (HCMV), HIV and lentiviruses, as well as with Listeria monocytogenes [10,11,12,13]
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