Monocytes activate natural killer cells via inflammasome-induced interleukin 18 in response to Hepatitis C virus replication

• Verfasst von: Serti, Elisavet [VerfasserIn]
• Verfasst von: Lohmann, Volker [VerfasserIn]
• Titel: Monocytes activate natural killer cells via inflammasome-induced interleukin 18 in response to Hepatitis C virus replication
• Verf.angabe: Elisavet Serti, Jens M. Werner, Michael Chattergoon, Andrea L. Cox, Volker Lohmann, and Barbara Rehermann
• E-Jahr: 2014
• Jahr: 28 March 2014
• Umfang: 15 S.
• Fussnoten: Gesehen am 21.08.2020
• Titel Quelle: Enthalten in: Gastroenterology
• Ort Quelle: Stanford, Calif. : HighWire Press, 1965
• Jahr Quelle: 2014
• Band/Heft Quelle: 147(2014), 1, Seite 209-220.e3
• ISSN Quelle: 1528-0012
• DOI: doi:10.1053/j.gastro.2014.03.046
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cytokine Production
• Sach-SW: Hepatocyte
• Sach-SW: Immune Response
• Sach-SW: Viral Replication
• K10plus-PPN: 1727599632

Abstract

Background & Aims - Production of interferon (IFN)-γ by natural killer (NK) cells is attenuated during chronic infection with hepatitis C virus (HCV). We investigated whether this is due to intrinsic or extrinsic mechanisms of NK cells. - Methods - Peripheral blood mononuclear cells (PBMCs) were collected from patients with chronic HCV infection or uninfected blood donors (controls); NK cells and monocytes were isolated or eliminated. We cultured hepatoma cells that express luciferase-tagged subgenomic HCV replicons (Huh7/HCV replicon cells) or their HCV-negative counterparts (Huh7) with NK cells in the presence or absence of other populations of PBMCs. Antiviral activity, cytotoxicity, and cytokine production were assessed. - Results - NK cells produced greater amounts of IFN-γ when PBMC were cocultured with Huh7/HCV replicon cells than with Huh7 cells; NK cells and PBMCs from controls suppressed HCV replication to a greater extent than those from patients with chronic HCV infection. This antiviral effect was predominantly mediated by tumor necrosis factor (TNF)-α and IFN-γ. The antiviral activity of NK cells and their production of IFN-γ were reduced when they were used in coculture alone (rather than with PBMC), or after depletion of CD14+ monocytes, after knockdown of the inflammasome in monocytes, or after neutralization of interleukin-18, which is regulated by the inflammasome. These findings indicate a role for monocytes in NK cell activation. Compared with control monocytes, monocytes from patients with chronic HCV infection had reduced TNF-α-mediated (direct) and reduced NK cell-mediated (indirect) antiviral effects. Control monocytes increased the antiviral effects of NK cells from patients with chronic HCV infection and their production of IFN-γ. - Conclusions - Monocytes sense cells that contain replicating HCV and respond by producing interleukin-18 via the inflammasome and by activating NK cells. Patients with chronic HCV infection have reduced monocyte function, attenuating NK cell IFN-γ-mediated responses.