Veritable antiviral capacity of natural killer cells in chronic HBV infection: an argument for an earlier anti-virus treatment

Xiaoyan Li,Yuehua Huang,Lin Gu,Yifan Lian,Liang Zhou,Yurong Gu,Lubiao Chen

doi:10.1186/s12967-017-1318-1

Abstract

BackgroundThere is limited information on innate immunity, especially natural killer (NK) cell function, in different chronic hepatitis B (CHB) stages. Therefore, we examined whether the clinical staging strategy accurately reflects veritable NK cell immunity.MethodsA total of 237 eligible CHB patients and 22 healthy controls were enrolled in our study. Demographic and clinical data were collected, and the CHB phases (immune active-IA, immune tolerant phase-IT, inactive CHB-IC, and grey zone-GZ) were classified according to the latest American Association for the Study of Liver Disease guidelines. Peripheral blood mononuclear cells from patients and healthy controls were tested for NK cell frequency, phenotype and function using flow cytometry.ResultsA significant decrease in activating receptor NKp44 and NKp46 expression and significant increase of exhaustion molecule Tim-3 expression were observed in NK cells from CHB patients. Reduced cytokine secretion and preserved or elevated cytotoxic function were also observed. Patients in the IT group exhibited comparable cytokine secretion and cytolytic capacity as age-matched IA patients. NK cell anti-viral functions were preserved in GZ patients. Some of the NK cell function in patients who were excluded from treatment by the current treatment guidelines was less compromised than patients who qualified for treatment.ConclusionOur findings provide evidence of veritable NK cell immunity during different natural history phases in treatment-naïve patients with chronic HBV Infection. Chronic HBV infection hindered NK cell function in CHB patients. However, the presumed IT and GZ statuses of CHB patients based on the clinical parameters may not accurately reflect the inner immune status of these patients and should be reconsidered. Some patients excluded from treatment by the current treatment guidelines may be able to be selected as candidates for treatment.

Highlights

There is limited information on innate immunity, especially natural killer (NK) cell function, in different chronic hepatitis B (CHB) stages
We detected the percentage of NK cells and their subsets in total lymphocytes from CHB patients in four clinical phases (IA, inactive CHB phase (IC), Immune tolerance (IT), and grey zone (GZ)) and healthy controls to investigate whether the distributions of total NK cells and their subsets change within distinct disease phases in treatment-naïve CHB
No significant differences in the percentages of total NK cells or their subsets were observed between CHB patients and healthy controls (Fig. 1b)

Summary

Introduction

There is limited information on innate immunity, especially natural killer (NK) cell function, in different chronic hepatitis B (CHB) stages. The innate and adaptive immune responses against HBV in chronic hepatitis B (CHB) patients are compromised [4]. Reports on receptor expression during chronic persistent HBV infection are inconsistent [7,8,9,10,11]. NK cells regulate the adaptive immune response by interacting with APCs and T cells, which affects the development of HBV infection [7]. Individuals who clear HBV during acute HBV infection exhibit good NK cell responses against HBV and express more activating receptors and fewer inhibitory receptors [13]. NK cell function is disrupted in patients with prolonged HBV infection, which weakens the eradication of HBV from the liver [14]

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Results

Discussion

Conclusion