Peripheral blood iNKT cell activation correlates with liver damage during acute hepatitis C.

Tina Senff,Georg M Lauer,Ruth Broering,Arthur Y Kim,Ulf Dittmer,Jörg Timm,Christine Cosmovici,Christopher Menne,Lia Laura Lewis-Ximenez,Jasneet Aneja,Norbert Scherbaum,Astrid M Westendorf

doi:10.1172/jci.insight.155432

Abstract

Invariant NK T (iNKT) cells are implicated in viral clearance; however, their role in hepatitis C virus (HCV) infection remains controversial. Here, iNKT cells were studied during different stages of HCV infection. iNKT cells from patients with acute HCV infection and people who inject drugs (PWID) with chronic or spontaneously resolved HCV infection were characterized by flow cytometry. In a longitudinal analysis during acute HCV infection, frequencies of activated CD38+ iNKT cells reproducibly declined in spontaneously resolving patients, whereas they were persistently elevated in patients progressing to chronic infection. During the first year of infection, the frequency of activated CD38+ or CD69+ iNKT cells strongly correlated with alanine transaminase levels with particularly pronounced correlations in spontaneously resolving patients. Increased frequencies of activated iNKT cells in chronic HCV infection were confirmed in cross-sectional analyses of PWID with chronic or spontaneously resolved HCV infection; however, no apparent functional differences were observed with various stimulation protocols. Our data suggest that iNKT cells are activated during acute hepatitis C and that activation is sustained in chronic infection. The correlation between the frequency of activated iNKT cells and alanine transaminase may point toward a role of iNKT cells in liver damage.

Highlights

Even though highly effective direct acting antivirals are available, hepatitis C virus (HCV)infection is still a major global healthcare problem with 71 million chronically infected individuals worldwide
The activation phenotype of circulating Invariant natural killer T (iNKT) cells associates with the outcome of Unlike T and NK cells, whose influence on the outcome of hepatitis C virus infection has been analyzed in great detail [20,21], little is known about a possible relationship between the phenotype and functionality of iNKT cells and HCV control
In order to elucidate the role of iNKT cells in different stages of HCV infection, we performed flow cytometric analysis on peripheral blood mononuclear cells (PBMCs) samples from patients with acute HCV infection over a time course of up to one year post estimated time of infection

Summary

Introduction

Even though highly effective direct acting antivirals are available, hepatitis C virus (HCV)infection is still a major global healthcare problem with 71 million chronically infected individuals worldwide. 60-80% of individuals with acute hepatitis C develop chronic infection defined as persistent viremia for more than six months after HCV exposure [1]. Genetic association studies as well as analysis of the phenotype and function of NK cells in HCV infected individuals have highlighted the importance of innate immune cells like NK cells for viral clearance. Due to their early activation after exposure, they have been implicated in the resolution of acute infection and might protect from persistent infection at an early stage prior to seroconversion [6,7,8,9]

Methods

Results

Conclusion