Expansion of dysfunctional CD56-CD16+ NK cells in chronic hepatitis B patients
Ratna S Wijaya 1 2 , Scott A Read 1 3 , Stephen Schibeci 1 , Shuanglin Han 1 , Mahmoud K Azardaryany 1 , David van der Poorten 4 , Rita Lin 4 , Lawrence Yuen 4 5 , Vincent Lam 4 5 , Mark W Douglas 1 4 6 , Jacob George 1 4 , Golo Ahlenstiel 1 3 7
Affiliations
Affiliations
1
Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia.
2
Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia.
3
Blacktown Clinical School, Western Sydney University, Blacktown, NSW, 2148, Australia.
4
Westmead Hospital, University of Sydney, Sydney, NSW, Australia.
5
Discipline of Surgery, University of Sydney, Sydney, Australia.
6
Centre for Infectious Diseases and Microbiology, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney at Westmead Hospital, Westmead, NSW, 2145, Australia.
7
Blacktown Hospital, Blacktown, NSW, 2148, Australia.
PMID: 33411395 DOI: 10.1111/liv.14784
Abstract
Background & aims: Natural killer (NK) cells are primary innate effector cells that play an important role in the control of human viral infections. During chronic viral infection, NK cells undergo significant changes in phenotype, function, and subset distribution, including the appearance of CD56-CD16+ (CD56-) NK cells, previously identified in chronic human immunodeficiency virus (HIV) and hepatitis C virus infection. However, the presence of CD56- NK cells in the pathogenesis of chronic hepatitis B (CHB) remains unknown.
Methods: Phenotype and function of CD56- NK cells from patients with CHB (n=28) were assessed using flow cytometry and in vitro stimulation with HBV antigen.
Results: CHB patients had a higher frequency of CD56- NK cells compared to healthy controls in peripheral blood (6.2 vs 1.4%, p<0.0001). Compared to CD56+ NK cells, CD56- NK cells had increased expression of inhibitory receptors, and reduced expression of activating receptors, as measured by MFI and qPCR. CD56- NK cells were less responsive to target cell and cytokine stimulation compared to their CD56+ counterparts. In addition, CD56- NK cells demonstrated defective dendritic cells (DCs) interactions resulting in reduced DCs maturation, lower expression of NK CD69, and impaired capacity of NK cells to eliminate immature DCs in co-culture studies. Finally, frequency of CD56- NK cells was positively correlated with serum HBV DNA levels.
Conclusion: Chronic HBV infection induces the expansion of highly dysfunctional of CD56- NK cells that likely contribute to inefficient innate and adaptive antiviral immune response in chronic HBV infection.
This article is protected by copyright. All rights reserved. 作者: StephenW 时间: 2021-1-10 09:23
慢性乙型肝炎患者功能障碍的CD56-CD16 + NK细胞的扩增
Ratna S Wijaya 1 2，Scott A Read 1 3，Stephen Schibeci 1，Shuanglin Han 1，Mahmoud K Azardaryany 1，David van der Poorten 4，Rita Lin 4，Lawrence Yuen 4 5，Vincent Lam 4 5，Mark W Douglas 1 4 6，雅各布·乔治1 4，戈洛·阿伦斯蒂尔1 3 7
隶属关系
隶属关系