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Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver
The ability of innate immune cells to sense and respond to impending danger varies by anatomical location. The liver is considered tolerogenic but is still capable of mounting a successful immune response to clear various infections. To understand whether hepatic immune cells tune their response to...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072808/ https://www.ncbi.nlm.nih.gov/pubmed/24967632 http://dx.doi.org/10.1371/journal.ppat.1004210 |
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author | Jo, Juandy Tan, Anthony T. Ussher, James E. Sandalova, Elena Tang, Xin-Zi Tan-Garcia, Alfonso To, Natalie Hong, Michelle Chia, Adeline Gill, Upkar S. Kennedy, Patrick T. Tan, Kai Chah Lee, Kang Hoe De Libero, Gennaro Gehring, Adam J. Willberg, Christian B. Klenerman, Paul Bertoletti, Antonio |
author_facet | Jo, Juandy Tan, Anthony T. Ussher, James E. Sandalova, Elena Tang, Xin-Zi Tan-Garcia, Alfonso To, Natalie Hong, Michelle Chia, Adeline Gill, Upkar S. Kennedy, Patrick T. Tan, Kai Chah Lee, Kang Hoe De Libero, Gennaro Gehring, Adam J. Willberg, Christian B. Klenerman, Paul Bertoletti, Antonio |
author_sort | Jo, Juandy |
collection | PubMed |
description | The ability of innate immune cells to sense and respond to impending danger varies by anatomical location. The liver is considered tolerogenic but is still capable of mounting a successful immune response to clear various infections. To understand whether hepatic immune cells tune their response to different infectious challenges, we probed mononuclear cells purified from human healthy and diseased livers with distinct pathogen-associated molecules. We discovered that only the TLR8 agonist ssRNA40 selectively activated liver-resident innate immune cells to produce substantial quantities of IFN-γ. We identified CD161(Bright) mucosal-associated invariant T (MAIT) and CD56(Bright) NK cells as the responding liver-resident innate immune cells. Their activation was not directly induced by the TLR8 agonist but was dependent on IL-12 and IL-18 production by ssRNA40-activated intrahepatic monocytes. Importantly, the ssRNA40-induced cytokine-dependent activation of MAIT cells mirrored responses induced by bacteria, i.e., generating a selective production of high levels of IFN-γ, without the concomitant production of TNF-α or IL-17A. The intrahepatic IFN-γ production could be detected not only in healthy livers, but also in HBV- or HCV-infected livers. In conclusion, the human liver harbors a network of immune cells able to modulate their immunological responses to different pathogen-associated molecules. Their ability to generate a strong production of IFN-γ upon stimulation with TLR8 agonist opens new therapeutic opportunities for the treatment of diverse liver pathologies. |
format | Online Article Text |
id | pubmed-4072808 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40728082014-07-02 Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver Jo, Juandy Tan, Anthony T. Ussher, James E. Sandalova, Elena Tang, Xin-Zi Tan-Garcia, Alfonso To, Natalie Hong, Michelle Chia, Adeline Gill, Upkar S. Kennedy, Patrick T. Tan, Kai Chah Lee, Kang Hoe De Libero, Gennaro Gehring, Adam J. Willberg, Christian B. Klenerman, Paul Bertoletti, Antonio PLoS Pathog Research Article The ability of innate immune cells to sense and respond to impending danger varies by anatomical location. The liver is considered tolerogenic but is still capable of mounting a successful immune response to clear various infections. To understand whether hepatic immune cells tune their response to different infectious challenges, we probed mononuclear cells purified from human healthy and diseased livers with distinct pathogen-associated molecules. We discovered that only the TLR8 agonist ssRNA40 selectively activated liver-resident innate immune cells to produce substantial quantities of IFN-γ. We identified CD161(Bright) mucosal-associated invariant T (MAIT) and CD56(Bright) NK cells as the responding liver-resident innate immune cells. Their activation was not directly induced by the TLR8 agonist but was dependent on IL-12 and IL-18 production by ssRNA40-activated intrahepatic monocytes. Importantly, the ssRNA40-induced cytokine-dependent activation of MAIT cells mirrored responses induced by bacteria, i.e., generating a selective production of high levels of IFN-γ, without the concomitant production of TNF-α or IL-17A. The intrahepatic IFN-γ production could be detected not only in healthy livers, but also in HBV- or HCV-infected livers. In conclusion, the human liver harbors a network of immune cells able to modulate their immunological responses to different pathogen-associated molecules. Their ability to generate a strong production of IFN-γ upon stimulation with TLR8 agonist opens new therapeutic opportunities for the treatment of diverse liver pathologies. Public Library of Science 2014-06-26 /pmc/articles/PMC4072808/ /pubmed/24967632 http://dx.doi.org/10.1371/journal.ppat.1004210 Text en © 2014 Jo 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 Jo, Juandy Tan, Anthony T. Ussher, James E. Sandalova, Elena Tang, Xin-Zi Tan-Garcia, Alfonso To, Natalie Hong, Michelle Chia, Adeline Gill, Upkar S. Kennedy, Patrick T. Tan, Kai Chah Lee, Kang Hoe De Libero, Gennaro Gehring, Adam J. Willberg, Christian B. Klenerman, Paul Bertoletti, Antonio Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver |
title | Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver |
title_full | Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver |
title_fullStr | Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver |
title_full_unstemmed | Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver |
title_short | Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver |
title_sort | toll-like receptor 8 agonist and bacteria trigger potent activation of innate immune cells in human liver |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072808/ https://www.ncbi.nlm.nih.gov/pubmed/24967632 http://dx.doi.org/10.1371/journal.ppat.1004210 |
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