Hepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A-mediated imbalance of inflammatory cytokines.

Understanding how hepatitis C virus (HCV) induces and circumvents the host's natural killer (NK) cell-mediated immunity is of critical importance in efforts to design effective therapeutics. We report here the decreased expression of the NKG2D activating receptor as a novel strategy adopted by...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Damien Sène, Franck Levasseur, Michal Abel, Marion Lambert, Xavier Camous, Céline Hernandez, Véronique Pène, Arielle R Rosenberg, Evelyne Jouvin-Marche, Patrice N Marche, Patrice Cacoub, Sophie Caillat-Zucman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7d4b8c71da6d4f89bb063c44cd7e01d1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7d4b8c71da6d4f89bb063c44cd7e01d1
record_format	dspace
spelling	oai:doaj.org-article:7d4b8c71da6d4f89bb063c44cd7e01d12021-11-18T06:05:19ZHepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A-mediated imbalance of inflammatory cytokines.1553-73661553-737410.1371/journal.ppat.1001184https://doaj.org/article/7d4b8c71da6d4f89bb063c44cd7e01d12010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21085608/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Understanding how hepatitis C virus (HCV) induces and circumvents the host's natural killer (NK) cell-mediated immunity is of critical importance in efforts to design effective therapeutics. We report here the decreased expression of the NKG2D activating receptor as a novel strategy adopted by HCV to evade NK-cell mediated responses. We show that chronic HCV infection is associated with expression of ligands for NKG2D, the MHC class I-related Chain (MIC) molecules, on hepatocytes. However, NKG2D expression is downmodulated on circulating NK cells, and consequently NK cell-mediated cytotoxic capacity and interferon-γ production are impaired. Using an endotoxin-free recombinant NS5A protein, we show that NS5A stimulation of monocytes through Toll-like Receptor 4 (TLR4) promotes p38- and PI3 kinase-dependent IL-10 production, while inhibiting IL-12 production. In turn, IL-10 triggers secretion of TGFβ which downmodulates NKG2D expression on NK cells, leading to their impaired effector functions. Moreover, culture supernatants of HCV JFH1 replicating Huh-7.5.1 cells reproduce the effect of recombinant NS5A on NKG2D downmodulation. Exogenous IL-15 can antagonize the TGFβ effect and restore normal NKG2D expression on NK cells. We conclude that NKG2D-dependent NK cell functions are modulated during chronic HCV infection, and demonstrate that this alteration can be prevented by exogenous IL-15, which could represent a meaningful adjuvant for therapeutic intervention.Damien SèneFranck LevasseurMichal AbelMarion LambertXavier CamousCéline HernandezVéronique PèneArielle R RosenbergEvelyne Jouvin-MarchePatrice N MarchePatrice CacoubSophie Caillat-ZucmanPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 11, p e1001184 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Damien Sène Franck Levasseur Michal Abel Marion Lambert Xavier Camous Céline Hernandez Véronique Pène Arielle R Rosenberg Evelyne Jouvin-Marche Patrice N Marche Patrice Cacoub Sophie Caillat-Zucman Hepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A-mediated imbalance of inflammatory cytokines.
description	Understanding how hepatitis C virus (HCV) induces and circumvents the host's natural killer (NK) cell-mediated immunity is of critical importance in efforts to design effective therapeutics. We report here the decreased expression of the NKG2D activating receptor as a novel strategy adopted by HCV to evade NK-cell mediated responses. We show that chronic HCV infection is associated with expression of ligands for NKG2D, the MHC class I-related Chain (MIC) molecules, on hepatocytes. However, NKG2D expression is downmodulated on circulating NK cells, and consequently NK cell-mediated cytotoxic capacity and interferon-γ production are impaired. Using an endotoxin-free recombinant NS5A protein, we show that NS5A stimulation of monocytes through Toll-like Receptor 4 (TLR4) promotes p38- and PI3 kinase-dependent IL-10 production, while inhibiting IL-12 production. In turn, IL-10 triggers secretion of TGFβ which downmodulates NKG2D expression on NK cells, leading to their impaired effector functions. Moreover, culture supernatants of HCV JFH1 replicating Huh-7.5.1 cells reproduce the effect of recombinant NS5A on NKG2D downmodulation. Exogenous IL-15 can antagonize the TGFβ effect and restore normal NKG2D expression on NK cells. We conclude that NKG2D-dependent NK cell functions are modulated during chronic HCV infection, and demonstrate that this alteration can be prevented by exogenous IL-15, which could represent a meaningful adjuvant for therapeutic intervention.
format	article
author	Damien Sène Franck Levasseur Michal Abel Marion Lambert Xavier Camous Céline Hernandez Véronique Pène Arielle R Rosenberg Evelyne Jouvin-Marche Patrice N Marche Patrice Cacoub Sophie Caillat-Zucman
author_facet	Damien Sène Franck Levasseur Michal Abel Marion Lambert Xavier Camous Céline Hernandez Véronique Pène Arielle R Rosenberg Evelyne Jouvin-Marche Patrice N Marche Patrice Cacoub Sophie Caillat-Zucman
author_sort	Damien Sène
title	Hepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A-mediated imbalance of inflammatory cytokines.
title_short	Hepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A-mediated imbalance of inflammatory cytokines.
title_full	Hepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A-mediated imbalance of inflammatory cytokines.
title_fullStr	Hepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A-mediated imbalance of inflammatory cytokines.
title_full_unstemmed	Hepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A-mediated imbalance of inflammatory cytokines.
title_sort	hepatitis c virus (hcv) evades nkg2d-dependent nk cell responses through ns5a-mediated imbalance of inflammatory cytokines.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/7d4b8c71da6d4f89bb063c44cd7e01d1
work_keys_str_mv	AT damiensene hepatitiscvirushcvevadesnkg2ddependentnkcellresponsesthroughns5amediatedimbalanceofinflammatorycytokines AT francklevasseur hepatitiscvirushcvevadesnkg2ddependentnkcellresponsesthroughns5amediatedimbalanceofinflammatorycytokines AT michalabel hepatitiscvirushcvevadesnkg2ddependentnkcellresponsesthroughns5amediatedimbalanceofinflammatorycytokines AT marionlambert hepatitiscvirushcvevadesnkg2ddependentnkcellresponsesthroughns5amediatedimbalanceofinflammatorycytokines AT xaviercamous hepatitiscvirushcvevadesnkg2ddependentnkcellresponsesthroughns5amediatedimbalanceofinflammatorycytokines AT celinehernandez hepatitiscvirushcvevadesnkg2ddependentnkcellresponsesthroughns5amediatedimbalanceofinflammatorycytokines AT veroniquepene hepatitiscvirushcvevadesnkg2ddependentnkcellresponsesthroughns5amediatedimbalanceofinflammatorycytokines AT ariellerrosenberg hepatitiscvirushcvevadesnkg2ddependentnkcellresponsesthroughns5amediatedimbalanceofinflammatorycytokines AT evelynejouvinmarche hepatitiscvirushcvevadesnkg2ddependentnkcellresponsesthroughns5amediatedimbalanceofinflammatorycytokines AT patricenmarche hepatitiscvirushcvevadesnkg2ddependentnkcellresponsesthroughns5amediatedimbalanceofinflammatorycytokines AT patricecacoub hepatitiscvirushcvevadesnkg2ddependentnkcellresponsesthroughns5amediatedimbalanceofinflammatorycytokines AT sophiecaillatzucman hepatitiscvirushcvevadesnkg2ddependentnkcellresponsesthroughns5amediatedimbalanceofinflammatorycytokines
_version_	1718424612962828288

Hepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A-mediated imbalance of inflammatory cytokines.

Ejemplares similares