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...
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Public Library of Science (PLoS)
2014
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oai:doaj.org-article:1ce3d53305944d1fb13fd10bd9ab368c2021-11-11T06:06:08ZToll-like receptor 8 agonist and bacteria trigger potent activation of innate immune cells in human liver.1553-73661553-737410.1371/journal.ppat.1004210https://doaj.org/article/1ce3d53305944d1fb13fd10bd9ab368c2014-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24967632/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The 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.Juandy JoAnthony T TanJames E UssherElena SandalovaXin-Zi TangAlfonso Tan-GarciaNatalie ToMichelle HongAdeline ChiaUpkar S GillPatrick T KennedyKai Chah TanKang Hoe LeeGennaro De LiberoAdam J GehringChristian B WillbergPaul KlenermanAntonio BertolettiPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 6, p e1004210 (2014) |
| 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 Juandy Jo Anthony T Tan James E Ussher Elena Sandalova Xin-Zi Tang Alfonso Tan-Garcia Natalie To Michelle Hong Adeline Chia Upkar S Gill Patrick T Kennedy Kai Chah Tan Kang Hoe Lee Gennaro De Libero Adam J Gehring Christian B Willberg Paul Klenerman Antonio Bertoletti Toll-like receptor 8 agonist and bacteria trigger potent activation of innate immune cells in human liver. |
| 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 |
article |
| author |
Juandy Jo Anthony T Tan James E Ussher Elena Sandalova Xin-Zi Tang Alfonso Tan-Garcia Natalie To Michelle Hong Adeline Chia Upkar S Gill Patrick T Kennedy Kai Chah Tan Kang Hoe Lee Gennaro De Libero Adam J Gehring Christian B Willberg Paul Klenerman Antonio Bertoletti |
| author_facet |
Juandy Jo Anthony T Tan James E Ussher Elena Sandalova Xin-Zi Tang Alfonso Tan-Garcia Natalie To Michelle Hong Adeline Chia Upkar S Gill Patrick T Kennedy Kai Chah Tan Kang Hoe Lee Gennaro De Libero Adam J Gehring Christian B Willberg Paul Klenerman Antonio Bertoletti |
| author_sort |
Juandy Jo |
| title |
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_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_sort |
toll-like receptor 8 agonist and bacteria trigger potent activation of innate immune cells in human liver. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/1ce3d53305944d1fb13fd10bd9ab368c |
| work_keys_str_mv |
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| _version_ |
1718439468170477568 |