| Online-Ressource |
Verfasst von: | Pollmann, Julia [VerfasserIn]  |
| Rupp, Daniel [VerfasserIn]  |
| Grünvogel, Oliver [VerfasserIn]  |
| Mutz, Pascal [VerfasserIn]  |
| Lasitschka, Felix [VerfasserIn]  |
| Lohmann, Volker [VerfasserIn]  |
| Bartenschlager, Ralf [VerfasserIn]  |
| 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 |
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. |
DOI: | doi:10.1016/j.jhep.2017.10.021 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: http://dx.doi.org/10.1016/j.jhep.2017.10.021 |
| Volltext: http://www.sciencedirect.com/science/article/pii/S0168827817324005 |
| DOI: https://doi.org/10.1016/j.jhep.2017.10.021 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Hepatitis C virus |
| Natural killer cells |
| NK cell-monocyte crosstalk |
| OX40 |
| OX40L |
K10plus-PPN: | 1576396886 |
Verknüpfungen: | → Zeitschrift |
Hepatitis C virus-induced natural killer cell proliferation involves monocyte-derived cells and the OX40/OX40L axis / Pollmann, Julia [VerfasserIn]; 2018 (Online-Ressource)