دورية أكاديمية
Toll-like receptor 8 agonist and bacteria trigger potent activation of innate immune cells in human liver.
| العنوان: | Toll-like receptor 8 agonist and bacteria trigger potent activation of innate immune cells in human liver. |
|---|---|
| المؤلفون: | 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 |
| المصدر: | PLoS Pathogens, Vol 10, Iss 6, p e1004210 (2014) |
| بيانات النشر: | Public Library of Science (PLoS), 2014. |
| سنة النشر: | 2014 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| Relation: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24967632/pdf/?tool=EBI; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1004210 |
| URL الوصول: | https://doaj.org/article/1ce3d53305944d1fb13fd10bd9ab368c |
| رقم الأكسشن: | edsdoj.1ce3d53305944d1fb13fd10bd9ab368c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537366 15537374 |
|---|---|
| DOI: | 10.1371/journal.ppat.1004210 |