Activation of TNF-α-AID axis and co-inhibitory signals in coordination with Th1-type immunity in a mouse model recapitulating hepatitis B.
Antiviral Res
; 139: 138-145, 2017 Mar.
Article
em En
| MEDLINE
| ID: mdl-28063995
ABSTRACT
Hepatitis B virus (HBV) infection evokes host immune responses that primarily determine the outcome of HBV infection and the clinical features of HBV-associated liver disease. The precise mechanisms by which host factors restrict HBV replication, however, are poorly understood due to the lack of useful animal models that recapitulate immune responses to HBV. Here, we performed comprehensive immunologic gene expression profiling of the liver of a mouse model recapitulating anti-HBV immune response using a high sensitivity direct digital counting system. Anti-HBV cellular immunity with liver inflammation was elicited in mice hydrodynamically injected with a CpG-depleted plasmid encoding hepatitis B surface antigen (HBsAg) gene after preimmunization with HBsAg vaccine. Comprehensive expression analyses revealed the upregulation of Th1-associated genes including tumor necrosis factor (Tnf) and negative regulators of T cell function in the inflamed liver. Interestingly, activation-induced cytidine deaminase (Aicda, termed AID in humans), which reportedly suppresses HBV infection in vitro, was upregulated in hepatocytes in the course of anti-HBV immunity. Hepatocytic expression of Aicda in a Tnf-dependent manner was confirmed by the administration of Tnf antagonist into Aicda-tdTomato mice with anti-HBV immunity. Our findings suggest that activation of Tnf-Aicda axis and co-inhibitory signals to T cells in coordination with Th1-type immunity has critical roles in the immune response against HBV infection.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fator de Necrose Tumoral alfa
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Células Th1
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Citidina Desaminase
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Hepatite B
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Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Antiviral Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão