Objective To explore the role of MyD88 signaling in MHV-3 virus-mediated fulminant hepatitis. Methods We evaluated liver lesion status, the expression of multiple pro-inflammatory cytokines and HMGB1, the recruitment ...Objective To explore the role of MyD88 signaling in MHV-3 virus-mediated fulminant hepatitis. Methods We evaluated liver lesion status, the expression of multiple pro-inflammatory cytokines and HMGB1, the recruitment of inflammatory ILC3, and mortality in MyD88-/-and WT mice. Results The expression of multiple pro-inflammatory cytokines that recruit inflammatory ILC3 to the liver was severely impaired in MyD88-/-mice resulting in reduced liver pathology, viral replication, and mortality post-infection. Additionally, MHV-3 markedly increased the expression of high-mobility group box 1(HMGB1) in infected hepatocytes/macrophages and induced HMGB1 protein migration from the nucleus to the extracellular milieu, where it activates MyD88-dependent inflammation. Conclusion Our findings indicate that MyD88 exacerbates immunological pathology in experimental viral fulminant hepatitis.展开更多
基金Supported by grants from the National Natural Sciences Foundation of China(No.81361120400 and 81222023)
文摘Objective To explore the role of MyD88 signaling in MHV-3 virus-mediated fulminant hepatitis. Methods We evaluated liver lesion status, the expression of multiple pro-inflammatory cytokines and HMGB1, the recruitment of inflammatory ILC3, and mortality in MyD88-/-and WT mice. Results The expression of multiple pro-inflammatory cytokines that recruit inflammatory ILC3 to the liver was severely impaired in MyD88-/-mice resulting in reduced liver pathology, viral replication, and mortality post-infection. Additionally, MHV-3 markedly increased the expression of high-mobility group box 1(HMGB1) in infected hepatocytes/macrophages and induced HMGB1 protein migration from the nucleus to the extracellular milieu, where it activates MyD88-dependent inflammation. Conclusion Our findings indicate that MyD88 exacerbates immunological pathology in experimental viral fulminant hepatitis.
