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Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver Inflammation

Natural killer (NK) cells play an important role in hepatitis B virus (HBV) infection control, and are regulated by a complex network of activating and inhibitory receptors. However, NK cell activity in HBV patients remains poorly understood. The objective of this study was to investigate the phenot...

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Autores principales: Li, Wanyu, Jiang, Yanfang, Wang, Xiaomei, Jin, Jinglan, Qi, Yue, Chi, Xiumei, Zhang, Hong, Feng, Xiangwei, Niu, Junqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546267/
https://www.ncbi.nlm.nih.gov/pubmed/26291078
http://dx.doi.org/10.1371/journal.pone.0135874
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author Li, Wanyu
Jiang, Yanfang
Wang, Xiaomei
Jin, Jinglan
Qi, Yue
Chi, Xiumei
Zhang, Hong
Feng, Xiangwei
Niu, Junqi
author_facet Li, Wanyu
Jiang, Yanfang
Wang, Xiaomei
Jin, Jinglan
Qi, Yue
Chi, Xiumei
Zhang, Hong
Feng, Xiangwei
Niu, Junqi
author_sort Li, Wanyu
collection PubMed
description Natural killer (NK) cells play an important role in hepatitis B virus (HBV) infection control, and are regulated by a complex network of activating and inhibitory receptors. However, NK cell activity in HBV patients remains poorly understood. The objective of this study was to investigate the phenotypic and functional characteristics of circulating NK cells in patients during different chronic hepatitis B (CHB) infection stages. We investigated NK cell phenotypes, receptor expression and function in 86 CHB patients and 20 healthy controls. NK cells were purified and NK cell subsets were characterized by flow cytometry. Cytotoxic activity (CD107a) and interferon-gamma (IFN-γ) secretion were examined, and Natural Killer p46 (NKP46) blockade and spontaneous NK cell cytolytic activity against K562, HepG2 and HepG2.215 cell lines was studied. Activating NKp46 receptor expression was higher in inactive HBsAg carriers when compared with other groups (p = 0.008). NKp46 expression negatively correlated with HBV DNA (R = -0.253, p = 0.049) and ALT (R = -0.256, p = 0.045) levels. CD107a was higher in immune-activated groups when compared with immune-tolerant groups (p = 0.039). CD107a expression was related to viral load (p = 0.02) and HBeAg status (p = 0.024). In vitro NKp46 blockade reduced NK cell cytolytic activity against HepG2 and HepG2.215 cell lines (p = 0.02; p = 0.039). Furthermore, NK cells from high viral load CHB patients displayed significantly lower specific cytolytic activity against anti-NKp46-loaded K562 targets (p = 0.0321). No significant differences were observed in IFN-γ secretion (p > 0.05). In conclusion, NKp46 expression regulates NK cell cytolytic function. NKp46 may moderate NK cell activity during HBV replication suppression and HBV-associated liver damage and may be critical for NK cell activity during CHB infection.
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spelling pubmed-45462672015-08-26 Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver Inflammation Li, Wanyu Jiang, Yanfang Wang, Xiaomei Jin, Jinglan Qi, Yue Chi, Xiumei Zhang, Hong Feng, Xiangwei Niu, Junqi PLoS One Research Article Natural killer (NK) cells play an important role in hepatitis B virus (HBV) infection control, and are regulated by a complex network of activating and inhibitory receptors. However, NK cell activity in HBV patients remains poorly understood. The objective of this study was to investigate the phenotypic and functional characteristics of circulating NK cells in patients during different chronic hepatitis B (CHB) infection stages. We investigated NK cell phenotypes, receptor expression and function in 86 CHB patients and 20 healthy controls. NK cells were purified and NK cell subsets were characterized by flow cytometry. Cytotoxic activity (CD107a) and interferon-gamma (IFN-γ) secretion were examined, and Natural Killer p46 (NKP46) blockade and spontaneous NK cell cytolytic activity against K562, HepG2 and HepG2.215 cell lines was studied. Activating NKp46 receptor expression was higher in inactive HBsAg carriers when compared with other groups (p = 0.008). NKp46 expression negatively correlated with HBV DNA (R = -0.253, p = 0.049) and ALT (R = -0.256, p = 0.045) levels. CD107a was higher in immune-activated groups when compared with immune-tolerant groups (p = 0.039). CD107a expression was related to viral load (p = 0.02) and HBeAg status (p = 0.024). In vitro NKp46 blockade reduced NK cell cytolytic activity against HepG2 and HepG2.215 cell lines (p = 0.02; p = 0.039). Furthermore, NK cells from high viral load CHB patients displayed significantly lower specific cytolytic activity against anti-NKp46-loaded K562 targets (p = 0.0321). No significant differences were observed in IFN-γ secretion (p > 0.05). In conclusion, NKp46 expression regulates NK cell cytolytic function. NKp46 may moderate NK cell activity during HBV replication suppression and HBV-associated liver damage and may be critical for NK cell activity during CHB infection. Public Library of Science 2015-08-20 /pmc/articles/PMC4546267/ /pubmed/26291078 http://dx.doi.org/10.1371/journal.pone.0135874 Text en © 2015 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Li, Wanyu
Jiang, Yanfang
Wang, Xiaomei
Jin, Jinglan
Qi, Yue
Chi, Xiumei
Zhang, Hong
Feng, Xiangwei
Niu, Junqi
Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver Inflammation
title Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver Inflammation
title_full Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver Inflammation
title_fullStr Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver Inflammation
title_full_unstemmed Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver Inflammation
title_short Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver Inflammation
title_sort natural killer p46 controls hepatitis b virus replication and modulates liver inflammation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546267/
https://www.ncbi.nlm.nih.gov/pubmed/26291078
http://dx.doi.org/10.1371/journal.pone.0135874
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