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NK Cells in Ascites From Liver Disease Patients Display a Particular Phenotype and Take Part in Antibacterial Immune Response

Background and Aims: Ascites and spontaneous bacterial peritonitis (SBP) are frequent complications of liver cirrhosis. In spite of the clinical impact, knowledge about ascites as an immune cell compartment in liver disease is limited. Therefore, we analyzed NK cells in blood, ascites, and liver. Me...

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Autores principales: Lutz, Philipp, Jeffery, Hannah C., Jones, Nicholas, Birtwistle, Jane, Kramer, Benjamin, Nattermann, Jacob, Spengler, Ulrich, Strassburg, Christian P., Adams, David H., Oo, Ye H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694841/
https://www.ncbi.nlm.nih.gov/pubmed/31440239
http://dx.doi.org/10.3389/fimmu.2019.01838
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author Lutz, Philipp
Jeffery, Hannah C.
Jones, Nicholas
Birtwistle, Jane
Kramer, Benjamin
Nattermann, Jacob
Spengler, Ulrich
Strassburg, Christian P.
Adams, David H.
Oo, Ye H.
author_facet Lutz, Philipp
Jeffery, Hannah C.
Jones, Nicholas
Birtwistle, Jane
Kramer, Benjamin
Nattermann, Jacob
Spengler, Ulrich
Strassburg, Christian P.
Adams, David H.
Oo, Ye H.
author_sort Lutz, Philipp
collection PubMed
description Background and Aims: Ascites and spontaneous bacterial peritonitis (SBP) are frequent complications of liver cirrhosis. In spite of the clinical impact, knowledge about ascites as an immune cell compartment in liver disease is limited. Therefore, we analyzed NK cells in blood, ascites, and liver. Methods: Mononuclear cells from blood, ascites, and liver explants of patients with advanced liver disease were extracted by density gradient centrifugation. Phenotyping and analysis of functional responses were carried out using flow cytometry. Migratory potential was investigated with transwell chamber assays. NK cell metabolism was assessed by Seahorse technology. Results: NK cell frequency was increased in uninfected ascites compared to blood, but not to liver. Ascites NK cells were predominantly CD16(positive). CD56(bright) ascites NK cells did not share the typical phenotype of their liver counterparts. In contrast to the inhibitory receptor NKG2A, expression of the activating receptor NKG2D was decreased on ascites and liver CD16(positive) NK cells. Ascites NK cells expressed higher levels of CXCR3 than blood or liver NK cells, corresponding to increased ascites levels of CXCL10. Blood NK cells migrated toward ascites. Stimulation of mononuclear cells with Escherichia coli led to downregulation of NKG2D expression and IL-12 and IL-18 mediated secretion of interferon-γ by ascites and liver, but not blood NK cells. In-vivo, ascites NK cells expressed higher levels of the activation marker CD69 and lower levels of NKG2D during SBP compared to uninfected ascites. Conclusion: Ascites NK cells display a particular phenotype and are implicated in local immune defense against translocating bacteria.
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spelling pubmed-66948412019-08-22 NK Cells in Ascites From Liver Disease Patients Display a Particular Phenotype and Take Part in Antibacterial Immune Response Lutz, Philipp Jeffery, Hannah C. Jones, Nicholas Birtwistle, Jane Kramer, Benjamin Nattermann, Jacob Spengler, Ulrich Strassburg, Christian P. Adams, David H. Oo, Ye H. Front Immunol Immunology Background and Aims: Ascites and spontaneous bacterial peritonitis (SBP) are frequent complications of liver cirrhosis. In spite of the clinical impact, knowledge about ascites as an immune cell compartment in liver disease is limited. Therefore, we analyzed NK cells in blood, ascites, and liver. Methods: Mononuclear cells from blood, ascites, and liver explants of patients with advanced liver disease were extracted by density gradient centrifugation. Phenotyping and analysis of functional responses were carried out using flow cytometry. Migratory potential was investigated with transwell chamber assays. NK cell metabolism was assessed by Seahorse technology. Results: NK cell frequency was increased in uninfected ascites compared to blood, but not to liver. Ascites NK cells were predominantly CD16(positive). CD56(bright) ascites NK cells did not share the typical phenotype of their liver counterparts. In contrast to the inhibitory receptor NKG2A, expression of the activating receptor NKG2D was decreased on ascites and liver CD16(positive) NK cells. Ascites NK cells expressed higher levels of CXCR3 than blood or liver NK cells, corresponding to increased ascites levels of CXCL10. Blood NK cells migrated toward ascites. Stimulation of mononuclear cells with Escherichia coli led to downregulation of NKG2D expression and IL-12 and IL-18 mediated secretion of interferon-γ by ascites and liver, but not blood NK cells. In-vivo, ascites NK cells expressed higher levels of the activation marker CD69 and lower levels of NKG2D during SBP compared to uninfected ascites. Conclusion: Ascites NK cells display a particular phenotype and are implicated in local immune defense against translocating bacteria. Frontiers Media S.A. 2019-08-07 /pmc/articles/PMC6694841/ /pubmed/31440239 http://dx.doi.org/10.3389/fimmu.2019.01838 Text en Copyright © 2019 Lutz, Jeffery, Jones, Birtwistle, Krämer, Nattermann, Spengler, Strassburg, Adams and Oo. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lutz, Philipp
Jeffery, Hannah C.
Jones, Nicholas
Birtwistle, Jane
Kramer, Benjamin
Nattermann, Jacob
Spengler, Ulrich
Strassburg, Christian P.
Adams, David H.
Oo, Ye H.
NK Cells in Ascites From Liver Disease Patients Display a Particular Phenotype and Take Part in Antibacterial Immune Response
title NK Cells in Ascites From Liver Disease Patients Display a Particular Phenotype and Take Part in Antibacterial Immune Response
title_full NK Cells in Ascites From Liver Disease Patients Display a Particular Phenotype and Take Part in Antibacterial Immune Response
title_fullStr NK Cells in Ascites From Liver Disease Patients Display a Particular Phenotype and Take Part in Antibacterial Immune Response
title_full_unstemmed NK Cells in Ascites From Liver Disease Patients Display a Particular Phenotype and Take Part in Antibacterial Immune Response
title_short NK Cells in Ascites From Liver Disease Patients Display a Particular Phenotype and Take Part in Antibacterial Immune Response
title_sort nk cells in ascites from liver disease patients display a particular phenotype and take part in antibacterial immune response
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694841/
https://www.ncbi.nlm.nih.gov/pubmed/31440239
http://dx.doi.org/10.3389/fimmu.2019.01838
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