The Influence of Hepatitis C Viral Loads on Natural Killer Cell Function
| Autor: | Sam Kung, Qian Li, Julia D. Rempel, Mark Collister, C.A. Ellison, Gerald Y. Minuk |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Programmed cell death Cytotoxicity Hepatitis C virus Cell NK cells medicine.disease_cause IFN-gamma 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Interferon PD-1 medicine business.industry Hepatitis C medicine.disease 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Original Article business Viral load medicine.drug |
| Zdroj: | Gastroenterology Research |
| ISSN: | 1918-2813 1918-2805 |
| Popis: | Background Hepatitis C virus (HCV) infection has a high rate of chronicity, attributable to its capacity to alter host immunity, including natural killer (NK) cell function. In this study, the interaction between NK cell activity and HCV viral load was investigated. Methods Peripheral blood NK cells were examined for cytotoxicity and interferon (IFN)-γ expression in HCV infected low (LVL, < 800,000 IU/mL, n = 10) and high (HVL, > 800,000 IU/mL, n = 13) viral load patient cohorts. Results Spontaneous NK cell cytotoxicity was more robust in the LVL cohort resulting in a negative correlation with viral loads (spontaneous, r = -0.437, P = 0.037; IFN-α activated, r = -0.372, P = 0.081). Although the percent of IFN-γ+ NK cells did not associate with viral load, within the LVL cohort there was a marked increase in IFN-γ+ NK cells upon IFN-α activation relative to medium alone (P < 0.01). To examine the inability of NK cells derived from HVL patients to be further activated, the expression of the exhaustion marker programmed cell death protein (PD)-1 was evaluated. PD-1 expression upon NK cell activation correlated with viral load (r = 0.649, P = 0.009). In addition, HCV proteins upregulated PD-1 expression in vitro (P < 0.05), suggesting that HCV can directly promote NK cell exhaustion. Cells from HVL patients were also more likely to produce IFN-γ in response to HCV core protein. The finding that NK cell PD-1 and IFN-γ expression are linked (r = 0.542, P < 0.05) suggests that increased IFN-γ levels may induce PD-1 as a negative feedback mechanism. Conclusions High HCV loads appear to promote NK exhaustion in chronic HCV infection. |
| Databáze: | OpenAIRE |
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