title: Synergy between TLR3 and IL-18 promotes IFN-γ dependent TRAIL expression in human liver NK cells.
abstract: Natural killer (NK) cells are a component of innate immunity against viral infections through their rapid cytotoxic activity and cytokine production. However, intra-hepatic NK cells' ability to respond to virus is still mostly unknown. Our results show that the synthetic dsRNA polyinosinic-polycytidylic acid (poly I:C), a mimic of a common product of viral infections, activates NK cells directly in the context of cytokines found in the liver, i.e.: poly I:C plus inflammatory cytokines (IL-18, IL-12, and IL-2) induced NK cell IFN-γ production and TRAIL expression, and anti-inflammatory cytokines (TGF-β and IL-10) inhibit NK cell IFN-γ production. Neutralization of IFN-γ blocks poly I:C plus inflammatory cytokines-induced NK cell TRAIL expression, suggesting that IFN-γ is an autocrine differentiation factor for these cells. A better understanding of the intra-hepatic NK cell activation against viral infection may help in the design of therapies and vaccines for the control of viral hepatitis.
authors.affiliation: Department of Surgery, Division of Solid Organ Transplantation and Hepatobiliary Surgery, University of Rochester Medical Center, Rochester, NY 14642, USA. Zhengkun_tu@urmc.rochester.edu
authors.forename: Zhengkun
authors.initials: Z
authors.lastname: Tu
authors.forename: Heli K
authors.initials: HK
authors.lastname: Hamalainen-Laanaya
authors.forename: Ian Nicholas
authors.initials: IN
authors.lastname: Crispe
authors.forename: Mark S
authors.initials: MS
authors.lastname: Orloff
mesh_terms: D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016753:Interleukin-10 / Q000008:administration & dosage / Q000378:metabolism; D053765:Interleukin-12 Subunit p35 / Q000008:administration & dosage / Q000378:metabolism; D020382:Interleukin-18 / Q000008:administration & dosage / Q000378:metabolism*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D011070:Poly I-C / Q000008:administration & dosage / Q000494:pharmacology; D011994:Recombinant Proteins / Q000008:administration & dosage; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000378:metabolism
chemical_list: C508609:IL10 protein, human; C508858:IL12A protein, human; C508594:IL2 protein, human; D053765:Interleukin-12 Subunit p35; D020382:Interleukin-18; D007376:Interleukin-2; D011994:Recombinant Proteins; C495344:TLR3 protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051196:Toll-Like Receptor 3; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma; D011070:Poly I-C