Hepatitis C virus-induced natural killer cell proliferation involves monocyte-derived cells and the OX40/OX40L axis

• Verfasst von: Pollmann, Julia [VerfasserIn]
• Verfasst von: Rupp, Daniel [VerfasserIn]
• Verfasst von: Grünvogel, Oliver [VerfasserIn]
• Verfasst von: Mutz, Pascal [VerfasserIn]
• Verfasst von: Lasitschka, Felix [VerfasserIn]
• Verfasst von: Lohmann, Volker [VerfasserIn]
• Verfasst von: Bartenschlager, Ralf [VerfasserIn]
• Verfasst von: Cerwenka, Adelheid [VerfasserIn]
• Titel: Hepatitis C virus-induced natural killer cell proliferation involves monocyte-derived cells and the OX40/OX40L axis
• Verf.angabe: Julia Pollmann, Jana-Julia Götz, Daniel Rupp, Otto Strauss, Markus Granzin, Oliver Grünvogel, Pascal Mutz, Catharina Kramer, Felix Lasitschka, Volker Lohmann, Niklas K. Björkström, Robert Thimme, Ralf Bartenschlager, Adelheid Cerwenka
• Jahr: 2018
• Umfang: 10 S.
• Fussnoten: Available online 1 November 2017 ; Gesehen am 15.06.2018
• Titel Quelle: Enthalten in: Journal of hepatology
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1985
• Jahr Quelle: 2018
• Band/Heft Quelle: 68(2018), 3, Seite 421-430
• ISSN Quelle: 1600-0641
• DOI: doi:10.1016/j.jhep.2017.10.021
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Hepatitis C virus
• Sach-SW: Natural killer cells
• Sach-SW: NK cell-monocyte crosstalk
• Sach-SW: OX40
• Sach-SW: OX40L
• K10plus-PPN: 1576396886

Abstract

Background & Aims Natural killer (NK) cells are found at increased frequencies in patients with hepatitis C virus (HCV). NK cell activation has been shown to correlate with HCV clearance and to predict a favourable treatment response. The aim of our study was to dissect mechanisms leading to NK cell activation and proliferation in response to HCV. Methods: NK cell phenotype, proliferation, and function were assessed after the 6-day co-culture of human peripheral blood mononuclear cells with either HCV replicon-containing HuH6 hepatoblastoma cells or HCV-infected HuH7.5 cells. The results obtained were confirmed by immunohistochemistry of liver biopsies from patients with HCV and from HCV-negative controls. Results: In HCV-containing co-cultures, a higher frequency of NK cells upregulated the expression of the high-affinity IL-2 receptor chain CD25, proliferated more rapidly, and produced higher amounts of interferon γ compared with NK cells from control co-cultures. This NK cell activation was dependent on IL-2, cell-cell contact-mediated signals, and HCV replicon-exposed monocytes. The tumour necrosis factor-receptor superfamily member OX40 was induced on the activated CD25± NK cell subset and this induction was abrogated by the depletion of CD14+ monocytes. Moreover, OX40L was upregulated on CD14± monocyte-derived cells co-cultured with HCV-containing cells and also observed in liver biopsies from patients with HCV. Importantly, blocking of the OX40/OX40L interaction abolished both NK cell activation and proliferation. Conclusions: Our results uncover a previously unappreciated cell-cell contact-mediated mechanism of NK cell activation and proliferation in response to HCV, mediated by monocyte-derived cells and the OX40/OX40L axis. These results reveal a novel mode of crosstalk between innate immune cells during viral infection. Lay summary: Using a cell-culture model of hepatitis C virus (HCV) infection, our study revealed that natural killer (NK) cells become activated and proliferate when they are co-cultured with HCV-containing liver cells. The mechanism of this activation involves crosstalk with other innate immune cells and a cell-cell contact interaction mediated by the cell surface molecules OX40 and OX40L. Our study reveals a novel pathway leading to NK cell proliferation and activation against virus-infected cells that might be of relevance in antiviral immunity.