MyD88 exacerbates immunological pathology in experimental viral fulminant hepatitis  

作　　者：Jianzhao Deng Qin Ning Weiming Yan Xuan Yang Lizhen Zhao Yuzhang Wu Bei Zhang 

机构地区：[1]Department of Immunology, Medical College of Qingdao University [2]Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology [3]Institute of Immunology, Army Medical University

出　　处：《Oncology and Translational Medicine》2019年第2期58-67,共10页肿瘤学与转化医学（英文版）

基　　金：Supported by grants from the National Natural Sciences Foundation of China(No.81361120400 and 81222023)

摘　　要：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.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.

关 键 词：MYD88 MHV-3 HMGB1 ILC3 

分 类 号：R[医药卫生]