Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver

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The ability of human pathogens, like HBV, HCV or Plasmodium spp. to infect the liver might be influenced by its tolerogenic features. However, hepatic tolerance is not absolute since protective immunity can be triggered. Our goal was to define how to deliberately elicit an intrahepatic protective immune response. To achieve this, we purified immune cells residing in the vascular bed of human livers and we probed their reactivity against different pathogen-associated molecules, mimicking signature components of viruses or bacteria. We found that robust production of anti-viral cytokine IFN-γ was induced only by the TLR8 agonist ssRNA40. Mechanistically, ssRNA40 triggered hepatic monocytes to produce IL-12 and IL-18 cytokines, which stimulated IFN-γ production by liver-resident CD161Bright MAIT and CD56Bright NK cells. We also demonstrated that ssRNA40-mediated activation could occur in pathologic (HBV- or HCV-chronically infected) livers and that a similar cytokine-mediated activation of intrahepatic cells could also be triggered upon bacterial infection. Thus, we showed that the liver immune cells can respond vigorously to specific pathogen-associated molecules. The selective production of IFN-γ by liver-resident cells could have therapeutic implications for the treatment of chronic liver infections.

Vyšlo v časopise: Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004210
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004210

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