Association among cytokine profiles of innate and adaptive immune responses and clinical-virological features in untreated patients with chronic hepatitis B

Yurong Gu,Yuehua Huang,Lin Gu,Qiaolan Zheng,Yuankai Wu,Jing Li,Yifan Lian,Yanhua Bi,Yanlin Huang,Lubiao Chen,Zexuan Huang

doi:10.1186/s12879-020-05233-x

Abstract

BackgroundComplete clearance of intracellular viruses depends on effector cells of innate and adaptive immune systems. This study aimed to identify the relationships among antiviral cytokines produced by natural killer (NK) and T cells and clinical-virological characteristics in untreated chronic hepatitis B (CHB) patients.MethodsWe measured antiviral cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) produced by T, NK and natural killer T (NKT) cells, respectively, in a cohort with chronic hepatitis B virus (HBV) infection (CHB). We also correlated these cytokines with clinical-virological characteristics using a linear regression model.Resultslevels of IFN-γ+ and TNF-α+ CD4+ and CD8+ T cells were significantly higher in immune active (IA) phase than in other phases. Immune tolerant (IT) patients showed the lowest expression of IFN-γ by NK and NKT cells, and TNF-α by NK cells. IFN-γ+, TNF-α+ and IL-2+ CD4+ and CD8+ T cells frequencies were similar between IA and gray zone (GZ) phases. Principal component analysis based on cytokines confirmed that most IT patients significantly differed from inactive carriers (IC) and IA patients, while GZ patients were widely scattered. Multivariate analysis showed both T and NK cells producing IFN-γ and TNF-α, but not IL-2, had significant association with serum alanine aminotransferase (ALT). Moreover, IFN-γ+ NKT cells were associated with HBV DNA, while IFN-γ+ CD4+ and CD8+ T cells were correlated with age.ConclusionHBV clinical phases are characterized by distinct cytokine signatures, which showed relationship to viral features in these untreated CHB patients.

Highlights

Complete clearance of intracellular viruses depends on effector cells of innate and adaptive immune systems
Owing to the stringent definition criteria, differences in age, Alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA levels were observed between clinical phases
Cytokine profiles in chronic hepatitis B (CHB) patients with different stages of disease To investigate whether CHB patients beyond current treatment criteria are characterized by a state of defective antiviral response, we analyzed the expression profiles of three major effector cytokines, IFN-γ, Tumor necrosis factor-alpha (TNFα) and IL-2, produced by innate and adaptive immunity

Summary

Introduction

Complete clearance of intracellular viruses depends on effector cells of innate and adaptive immune systems. Chronic infection with hepatitis B virus (HBV) is estimated to affect more than 240 million people worldwide, leading to 620,000 deaths per year [1, 2]. HBV must recognize and bind to specific receptors, and enter the liver cells and migrate into the nucleus. In acute HBV infection, the host recognizes the virus and efficiently clears it as quickly as possible by a protective immune response [8,9,10]. Both of the innate and adaptive immunity play a critical role in fighting against HBV [11]

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