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+/dimCD16+—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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Acknowledgements
This work was supported by the National Natural Science of China (81271826, 31100126), the National Science Foundation of Beijing (7122108), SKLID development grant (2011SKLID207) and grants from the National S&T Major Project for Infectious Diseases (2012ZX10002003 and 2012ZX10002005).
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Zheng, J., Liang, H., Xu, C. et al. An unbalanced PD-L1/CD86 ratio in CD14++CD16+ monocytes is correlated with HCV viremia during chronic HCV infection. Cell Mol Immunol 11, 294–304 (2014). https://doi.org/10.1038/cmi.2013.70
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DOI: https://doi.org/10.1038/cmi.2013.70
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