Functions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis C.
During chronic hepatitis C virus (HCV) infection, the role of intra-hepatic (IH) natural killer (NK) cells is still controversial. To clarify their functions, we investigated anti-viral and cytotoxic activity of NK cells in human fresh liver biopsies. We compared the functions of IH-NK cells in HCV-...
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2014
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oai:doaj.org-article:e17a0f2eda5d47be81117b415e4f358f2021-11-18T08:21:50ZFunctions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis C.1932-620310.1371/journal.pone.0095614https://doaj.org/article/e17a0f2eda5d47be81117b415e4f358f2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24759660/?tool=EBIhttps://doaj.org/toc/1932-6203During chronic hepatitis C virus (HCV) infection, the role of intra-hepatic (IH) natural killer (NK) cells is still controversial. To clarify their functions, we investigated anti-viral and cytotoxic activity of NK cells in human fresh liver biopsies. We compared the functions of IH-NK cells in HCV-infected and NASH patients in physiological conditions as well as after stimulation using flow cytometric and immunohistochemical analyses. Interestingly, few IH-NK cells produced anti-viral cytokine IFN-γ in HCV-infected patients similarly as in non-infected individuals. Spontaneous degranulation activity was extremely low in peripheral NK cells compared to IH-NK cells, and was significantly higher in IH-NK cells from HCV-infected patients compared to non-infected individuals. Immunohistochemical analysis revealed that perforin granules were polarized at the apical pole of IH-NK cells. The presence of CD107a and perforin in IH-NK cells demonstrated that NK cells exerted a cytolytic activity at the site of infection. Importantly, IH-NK cell functions from HCV-infected patients were inducible by specific exogenous stimulations. Upon ex vivo K562 target cell stimulations, the number of degranulating NK cells was significantly increased in the pool of IH-NK cells compared to circulating NK cells. Interestingly, after stimulation, the frequency of IFN-γ-producing IH-NK cells in HCV-infected patients was significantly higher at early stage of inflammation whereas the spontaneous IH-NK cell degranulation activity was significantly impaired in patients with highest inflammation and fibrosis Metavir scores. Our study highlights that some IH-NK cells in HCV-infected patients are able to produce INF-γ and degranulate and that those two activities depend on liver environment including the severity of liver injury. Thus, we conclude that critical roles of IH-NK cells have to be taken into account in the course of the liver pathogenesis associated to chronic HCV infection.Emilie FugierHélène MarcheMarie-Ange ThéluZuzana Macek JílkováNicolas Van CampenhoutTania Dufeu-DuchesneVincent LeroyJean-Pierre ZarskiNathalie SturmPatrice N MarcheEvelyne Jouvin-MarchePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e95614 (2014) |
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Medicine R Science Q Emilie Fugier Hélène Marche Marie-Ange Thélu Zuzana Macek Jílková Nicolas Van Campenhout Tania Dufeu-Duchesne Vincent Leroy Jean-Pierre Zarski Nathalie Sturm Patrice N Marche Evelyne Jouvin-Marche Functions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis C. |
| description |
During chronic hepatitis C virus (HCV) infection, the role of intra-hepatic (IH) natural killer (NK) cells is still controversial. To clarify their functions, we investigated anti-viral and cytotoxic activity of NK cells in human fresh liver biopsies. We compared the functions of IH-NK cells in HCV-infected and NASH patients in physiological conditions as well as after stimulation using flow cytometric and immunohistochemical analyses. Interestingly, few IH-NK cells produced anti-viral cytokine IFN-γ in HCV-infected patients similarly as in non-infected individuals. Spontaneous degranulation activity was extremely low in peripheral NK cells compared to IH-NK cells, and was significantly higher in IH-NK cells from HCV-infected patients compared to non-infected individuals. Immunohistochemical analysis revealed that perforin granules were polarized at the apical pole of IH-NK cells. The presence of CD107a and perforin in IH-NK cells demonstrated that NK cells exerted a cytolytic activity at the site of infection. Importantly, IH-NK cell functions from HCV-infected patients were inducible by specific exogenous stimulations. Upon ex vivo K562 target cell stimulations, the number of degranulating NK cells was significantly increased in the pool of IH-NK cells compared to circulating NK cells. Interestingly, after stimulation, the frequency of IFN-γ-producing IH-NK cells in HCV-infected patients was significantly higher at early stage of inflammation whereas the spontaneous IH-NK cell degranulation activity was significantly impaired in patients with highest inflammation and fibrosis Metavir scores. Our study highlights that some IH-NK cells in HCV-infected patients are able to produce INF-γ and degranulate and that those two activities depend on liver environment including the severity of liver injury. Thus, we conclude that critical roles of IH-NK cells have to be taken into account in the course of the liver pathogenesis associated to chronic HCV infection. |
| format |
article |
| author |
Emilie Fugier Hélène Marche Marie-Ange Thélu Zuzana Macek Jílková Nicolas Van Campenhout Tania Dufeu-Duchesne Vincent Leroy Jean-Pierre Zarski Nathalie Sturm Patrice N Marche Evelyne Jouvin-Marche |
| author_facet |
Emilie Fugier Hélène Marche Marie-Ange Thélu Zuzana Macek Jílková Nicolas Van Campenhout Tania Dufeu-Duchesne Vincent Leroy Jean-Pierre Zarski Nathalie Sturm Patrice N Marche Evelyne Jouvin-Marche |
| author_sort |
Emilie Fugier |
| title |
Functions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis C. |
| title_short |
Functions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis C. |
| title_full |
Functions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis C. |
| title_fullStr |
Functions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis C. |
| title_full_unstemmed |
Functions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis C. |
| title_sort |
functions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis c. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/e17a0f2eda5d47be81117b415e4f358f |
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