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

摘要: The ability of innate immune cells to sense and respond impending danger varies by anatomical location. liver is considered tolerogenic but still capable mounting a successful response clear various infections. To understand whether hepatic tune their different infectious challenges, we probed mononuclear purified from human healthy diseased livers with distinct pathogen-associated molecules. We discovered that only the TLR8 agonist ssRNA40 selectively activated liver-resident produce substantial quantities IFN-γ. identified CD161(Bright) mucosal-associated invariant T (MAIT) CD56(Bright) NK as responding cells. Their activation was not directly induced dependent on IL-12 IL-18 production ssRNA40-activated intrahepatic monocytes. Importantly, ssRNA40-induced cytokine-dependent MAIT mirrored responses bacteria, i.e., generating selective high levels IFN-γ, without concomitant TNF-α or IL-17A. IFN-γ could be detected in livers, also HBV- HCV-infected livers. In conclusion, harbors network able modulate immunological generate strong upon stimulation opens new therapeutic opportunities for treatment diverse pathologies.