Natural Killer Cell Activation Status in Hepatitis C Virus Infection

Abstract

Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. It has been estimated that 180 million people are infected globally. Epidemiological data support a role for particular NK cell receptor bearing populations in the control of HCV infection, yet the mechanism by which NK cells respond to HCV early in infection is unknown. Perturbations of NK-DC interaction are likely to contribute to skewed fine-tuning of anti-HCV CD8+ and CD4+ T cell immune responses leading to ultimately to T cell dysfunction. The function of NK cells is regulated by a group of activating and inhibitory receptors, including NKp30, CD69 and KLRG-1 on NK cells. Activation of NK cells is primarily mediated by NCRs, as NKp30. Innate immune mechanisms suggested to have a role in editing of the adaptive immune response to intracellular pathogens include, among others, NK cell-mediated lysis of immature DCs, but not of mature ones, a function which relies almost entirely on NKp30 receptors. CD69 is a differentiation antigen expressed shortly after activation on T lymphocytes and other cells of haematopoietic origin, including NK cells. NK cells express CD69 after activation by different stimuli. It has been shown that CD69 triggers NK-cell-mediated cytolytic activity A subset of NK cells expresses the inhibitory killer cell lectin-like receptor G1 (KLRG1). KLRG1 expression is acquired during periods of NK cell division such as development and homeostatic proliferation. KLRG1+ NK cells are mature in phenotype, but show slower in vivo turnover rate, reduced proliferative response to IL-15, and poorer homeostatic expansion potential compared with mature NK cells lacking KLRG1. In the current study, we aimed to investigate the NK cell activation status in HCV infection and the role of this activation on the outcome of HCV infection whether clearance of the virus or inversely its persistence and chronicity. The study was conducted on 60 individuals who were classified into 3 groups; positive P.I HCWs, negative P.I healthy individuals & chronic HCV patients. The study showed a significant increase in percentage of NK cells, but not of NK-T cells, among positive P.I group than negative P.I and chronic HCV groups.