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CD69+NK cells contribute to the murine hepatitis virus strain 3-induced murine hepatitis
Lin Ding1, Tao Chen1, Xiao-Jing Wang1
1Department and Institute of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Abstract:
The role of hepatic CD69+ natural killer (NK) cells in virus-induced severe liver injury and subsequent hepatic failure is not well defined. In this study, a mouse model of fulminant liver failure (FHF) induced by murine hepatitis virus strain 3 (MHV-3) was used to study the role of hepatic CD69+NK cells in the development of FHF. The CD69 expression in NK cells in the liver, spleen, bone marrow and peripheral blood was detected by using flow cytometry. The correlation between the CD69 level in hepatic NK cells and liver injury was studied. The functional marker (CD107a), and activating and inhibitory receptor (NKG2D and NKG2A) expressed on CD69+NK cells and CD69-NK cells were detected by using flow cytometry. Pro-inflammatory cytokines (IL-9, IFN-γ and TNF-α) were also examined by using intracellular staining. After MHV-3 infection, the number of CD69+NK cells in the liver of BALB/cJ mice was increased markedly and peaked at 72 h post-infection. Similar changes were also observed in the spleen, bone marrow and peripheral blood. Meanwhile, the CD69 expression in hepatic NK cells was highly correlated with the serum level of ALT and AST. The expression of CD107a and NKG2D, as well as the production of TNF-α, IFN-γ and IL-9 in hepatic CD69+NK cells was all significantly up-regulated during 48-72 h post-infection. In contrast, the NKG2A expression was increased in hepatic CD69-NK cells but not in CD69+NK cells. These results suggested that hepatic CD69+NK cells play a pivotal role in the pathogenesis of FHF by enhancing degranulation and cytotoxic ability of NK cells and increasing the production of pro-inflammatory cytokines.
Insights
Hepatic CD69+ natural killer (NK) cells are crucial in severe liver injury. Their increased activity and pro-inflammatory cytokine production contribute to fulminant liver failure pathogenesis.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- The role of hepatic CD69+ natural killer (NK) cells in virus-induced severe liver injury and fulminant liver failure (FHF) remains unclear.
- Understanding these cells' function is vital for developing therapeutic strategies against liver failure.
Purpose of the Study:
- To investigate the role of hepatic CD69+ NK cells in the pathogenesis of FHF induced by murine hepatitis virus strain 3 (MHV-3).
- To analyze the expression of CD69 and associated functional markers on NK cells during MHV-3 infection.
Main Methods:
- Utilized a mouse model of FHF induced by MHV-3.
- Employed flow cytometry to detect CD69 expression, functional markers (CD107a), activating/inhibitory receptors (NKG2D, NKG2A) on NK cells.
- Assessed pro-inflammatory cytokines (IL-9, IFN-γ, TNF-α) via intracellular staining.
Main Results:
- MHV-3 infection significantly increased CD69+ NK cells in the liver, peaking at 72 hours post-infection.
- CD69 expression on hepatic NK cells correlated strongly with liver injury markers (ALT, AST).
- Hepatic CD69+ NK cells showed enhanced degranulation (CD107a), activating receptor (NKG2D) expression, and increased pro-inflammatory cytokine production (TNF-α, IFN-γ, IL-9).
Conclusions:
- Hepatic CD69+ NK cells play a critical role in FHF pathogenesis.
- These cells contribute to liver injury by enhancing NK cell cytotoxicity and promoting pro-inflammatory responses.
- Upregulation of NKG2A on CD69- NK cells suggests a regulatory mechanism during infection.
