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An unbalanced PD-L1/CD86 ratio in CD14(++)CD16(+) monocytes is correlated with HCV viremia during chronic HCV
Jiajia Zheng1, Hua Liang2, Chunhui Xu3
11] Department of Microbiology, Peking University Health Science Center, Beijing, China [2] Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China.
Insights
In chronic hepatitis C virus (HCV) infection, the CD14(++)CD16(+) monocyte subset is reduced and shows impaired immune function. This dysfunction correlates with HCV viral load, impacting disease progression.
Area of Science:
- Immunology
- Virology
- Hepatology
Background:
- Distinct circulating monocyte subsets are crucial in hepatitis C virus (HCV) infection pathogenesis.
- The specific roles and mechanisms of these monocyte subsets in HCV remain under-investigated.
Purpose of the Study:
- To analyze the distribution and phenotype of three monocyte subsets (CD14(++)CD16(-), CD14(++)CD16(+), CD14(+/dim)CD16(+)) in chronic HCV patients, spontaneous resolvers, and healthy controls.
- To evaluate the association between HCV viremia and disease progression by examining monocyte subset characteristics.
Main Methods:
- Flow cytometry was used to quantify and characterize circulating monocyte subsets.
- Analysis included expression levels of CD14, CD16, PD-L1, and CD86.
- Correlation analyses were performed between monocyte subset frequencies/phenotypes and HCV RNA/core antigen levels.
Main Results:
- The CD14(++)CD16(+) monocyte subset frequency was decreased in chronic HCV patients, correlating negatively with HCV RNA and core antigen levels.
- Higher PD-L1 expression and PD-L1/CD86 ratio were observed in CD14(++)CD16(+) monocytes from chronic HCV patients compared to controls.
- PD-L1 expression increased, while cytokine secretion decreased in CD14(++)CD16(+) monocytes upon TLR ligand and HCV JFH-1 stimulation.
Conclusions:
- Chronic HCV infection compromises the immune status of CD14(++)CD16(+) monocytes.
- The PD-L1/CD86 ratio in CD14(++)CD16(+) monocytes is linked to HCV viral load and core antigen levels.
- These findings highlight the specific role and significance of CD14(++)CD16(+) monocytes in chronic HCV pathogenesis.
Abstract:
Circulating monocyte subsets with distinct functions play important roles in hepatitis C virus (HCV) infection. However, the mechanisms have not been well studied. In this study, we analyzed the distributions and phenotypic characteristics of three circulating monocyte subsets-CD14(++)CD16(-), CD14(++)CD16(+) and CD14(+/dim)CD16(+)-in chronic HCV-infected patients, HCV spontaneous resolvers and healthy controls, and we evaluated the possible link between HCV viremia and disease progression. Our results indicated that the frequency of the CD14(++)CD16(+) monocyte subset was decreased, and negatively correlated with HCV RNA and core antigen levels during chronic HCV infection. PD-L1 expression and the PD-L1/CD86 ratio in CD14(++)CD16(+) monocytes were higher during chronic HCV infection than in spontaneous HCV resolvers and healthy controls. The PD-L1/CD86 ratio positively correlated with HCV viral load and core antigen levels. Finally, PD-L1 was significantly increased, while cytokine secretions were dramatically decreased upon Toll-like receptor (TLR) ligand binding and HCV JFH-1stimulation. These findings indicates the compromised immune status of the CD14(++)CD16(+) monocytes during chronic HCV infection and provides new insights into the specific role of the CD14(++)CD16(+) monocytes and their significance in chronic HCV infection.
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