Direct antiviral agents upregulate natural killer cell potential activity in chronic hepatitis C patients

Autor: Xiao-Xiao Wang, Haiying Zhang, Han-Ji Jiang, Bo Feng, Xu Cong, Xiangsha Kong, Hong Qin, Qian Jin, Lai Wei, Bi-Fen Luo
Rok vydání: 2019
Předmět:
Adult
Male
0301 basic medicine
Ledipasvir
medicine.medical_specialty
Time Factors
Sofosbuvir
Hepatitis C virus
medicine.disease_cause
Antiviral Agents
General Biochemistry
Genetics and Molecular Biology
Flow cytometry
Natural killer cell
Young Adult
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Humans
Longitudinal Studies
Receptor
Fluorenes
Innate immune system
Hematology
medicine.diagnostic_test
Natural Cytotoxicity Triggering Receptor 1
business.industry
General Medicine
Hepatitis C
Chronic
Middle Aged
Immunity
Innate
Killer Cells
Natural
030104 developmental biology
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
Immunology
Benzimidazoles
Female
NK Cell Lectin-Like Receptor Subfamily C
business
medicine.drug
Zdroj: Clinical and Experimental Medicine. 19:299-308
ISSN: 1591-9528
1591-8890
DOI: 10.1007/s10238-019-00564-9
Popis: Direct antiviral agents (DAAs) can eliminate hepatitis C virus rapidly and make chronic hepatitis C (CHC) curable. The changes in the innate immune system during treatment with DAAs are still in dispute. To investigate how the functions of natural killer (NK) cells change during and after treatment with DAAs in each NK cell subset. Thirteen CHC patients were treated with sofosbuvir/ledipasvir, and the expression levels of NKp46 and NKG2A were tested via flow cytometry at baseline, at 2, 4, 8 and 12 weeks during the therapy and 12 and 24 weeks after the end of treatment; expression levels were compared between CHC patients and 13 healthy controls. A redirected killing assay was used to detect the cytotoxicity of NK cells. After coculturing NK cells with JFH-Huh7 cells for 72 h, HCV RNA was tested to analyze the inhibition ability of NK cells. All patients achieved sustained virologic response. The expression of the activating receptor NKp46 was decreased first at week 8 during therapy with DAAs and then increased and normalized to levels in healthy controls after treatment with DAAs. The expression of the inhibitory receptor NKG2A was decreased during and after treatment with DAAs. Each NK cell subset has a similar changing trend during and after treatment with DAAs, although some differences can be found earlier and later. The ratio of NKp46 and NKG2A was upregulated after treatment with DAAs. CD56bright NK cells have less amplitude in the frequency ratio changes after treatment with DAAs. The coculture results showed that both the specific lysis and the inhibition of HCV replication were significantly upregulated after treatment with DAAs. DAA treatments can affect patients’ NK cell function. After DAA treatments, the expression of functional markers is downregulated, but the potential activity of NK cells is upregulated. The function of NK cells is normalized to levels in healthy controls. CD56bright NK cells play an important role in this process.
Databáze: OpenAIRE
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