Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More than in the Liver
Although epidemiological and functional studies have implicated NK cells in protection and early clearance of HCV, the mechanism by which they may contribute to viral control is poorly understood, particularly at the site of infection, the liver. We hypothesized that a unique immunophenotypic/functi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2014
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| Online Access: | http://hdl.handle.net/1721.1/90975 https://orcid.org/0000-0003-1570-9445 |
| _version_ | 1826205310055874560 |
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| author | Cosgrove, Cormac Berger, Christoph T. Kroy, Daniela C. Cheney, Patrick C. Ghebremichael, Musie Aneja, Jasneet Tomlinson, Michelle Kim, Arthur Y. Lauer, Georg M. Alter, Galit |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Cosgrove, Cormac Berger, Christoph T. Kroy, Daniela C. Cheney, Patrick C. Ghebremichael, Musie Aneja, Jasneet Tomlinson, Michelle Kim, Arthur Y. Lauer, Georg M. Alter, Galit |
| author_sort | Cosgrove, Cormac |
| collection | MIT |
| description | Although epidemiological and functional studies have implicated NK cells in protection and early clearance of HCV, the mechanism by which they may contribute to viral control is poorly understood, particularly at the site of infection, the liver. We hypothesized that a unique immunophenotypic/functional NK cell signature exists in the liver that may provide insights into the contribution of NK cells to viral control. Intrahepatic and blood NK cells were profiled from chronically infected HCV-positive and HCV-negative individuals. Baseline expression of activating and inhibitory receptors was assessed, as well as functional responses following stimulation through classic NK cell pathways. Independent of HCV infection, the liver was enriched for the immunoregulatory CD56[superscript bright] NK cell population, which produced less IFNγ and CD107a but comparable levels of MIP1β, and was immunophenotypically distinct from their blood counterparts. This profile was mostly unaltered in chronic HCV infection, though different expression levels of NKp46 and NKG2D were associated with different grades of fibrosis. In contrast to the liver, chronic HCV infection associated with an enrichment of CD161[superscript low]perforin[superscript high] NK cells in the blood correlated with increased AST and 2B4 expression. However, the association of relatively discrete changes in the NK cell phenotype in the liver with the fibrosis stage nevertheless suggests an important role for the NK response. Overall these data suggest that tissue localization has a more pervasive effect on NK cells than the presence of chronic viral infection, during which these cells might be mostly attuned to limiting immunopathology. It will be important to characterize NK cells during early HCV infection, when they should have a critical role in limiting infection. |
| first_indexed | 2024-09-23T13:10:40Z |
| format | Article |
| id | mit-1721.1/90975 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:10:40Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/909752022-09-28T12:25:16Z Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More than in the Liver Cosgrove, Cormac Berger, Christoph T. Kroy, Daniela C. Cheney, Patrick C. Ghebremichael, Musie Aneja, Jasneet Tomlinson, Michelle Kim, Arthur Y. Lauer, Georg M. Alter, Galit Massachusetts Institute of Technology. Department of Biological Engineering Ragon Institute of MGH, MIT and Harvard Alter, Galit Although epidemiological and functional studies have implicated NK cells in protection and early clearance of HCV, the mechanism by which they may contribute to viral control is poorly understood, particularly at the site of infection, the liver. We hypothesized that a unique immunophenotypic/functional NK cell signature exists in the liver that may provide insights into the contribution of NK cells to viral control. Intrahepatic and blood NK cells were profiled from chronically infected HCV-positive and HCV-negative individuals. Baseline expression of activating and inhibitory receptors was assessed, as well as functional responses following stimulation through classic NK cell pathways. Independent of HCV infection, the liver was enriched for the immunoregulatory CD56[superscript bright] NK cell population, which produced less IFNγ and CD107a but comparable levels of MIP1β, and was immunophenotypically distinct from their blood counterparts. This profile was mostly unaltered in chronic HCV infection, though different expression levels of NKp46 and NKG2D were associated with different grades of fibrosis. In contrast to the liver, chronic HCV infection associated with an enrichment of CD161[superscript low]perforin[superscript high] NK cells in the blood correlated with increased AST and 2B4 expression. However, the association of relatively discrete changes in the NK cell phenotype in the liver with the fibrosis stage nevertheless suggests an important role for the NK response. Overall these data suggest that tissue localization has a more pervasive effect on NK cells than the presence of chronic viral infection, during which these cells might be mostly attuned to limiting immunopathology. It will be important to characterize NK cells during early HCV infection, when they should have a critical role in limiting infection. National Institutes of Health (U.S.) (Grant U19 #AI08230) National Institutes of Health (U.S.) (Grant U19 #AI066345) 2014-10-20T12:29:51Z 2014-10-20T12:29:51Z 2014-08 2014-03 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/90975 Cosgrove, Cormac, Christoph T. Berger, Daniela C. Kroy, Patrick C. Cheney, Musie Ghebremichael, Jasneet Aneja, Michelle Tomlinson, Arthur Y. Kim, Georg M. Lauer, and Galit Alter. “Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More Than in the Liver.” Edited by Naglaa H. Shoukry. PLoS ONE 9, no. 8 (August 22, 2014): e105950. https://orcid.org/0000-0003-1570-9445 en_US http://dx.doi.org/10.1371/journal.pone.0105950 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science Public Library of Science |
| spellingShingle | Cosgrove, Cormac Berger, Christoph T. Kroy, Daniela C. Cheney, Patrick C. Ghebremichael, Musie Aneja, Jasneet Tomlinson, Michelle Kim, Arthur Y. Lauer, Georg M. Alter, Galit Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More than in the Liver |
| title | Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More than in the Liver |
| title_full | Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More than in the Liver |
| title_fullStr | Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More than in the Liver |
| title_full_unstemmed | Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More than in the Liver |
| title_short | Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More than in the Liver |
| title_sort | chronic hcv infection affects the nk cell phenotype in the blood more than in the liver |
| url | http://hdl.handle.net/1721.1/90975 https://orcid.org/0000-0003-1570-9445 |
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