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Status: Bibliographieeintrag

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Verfasst von:Pollmann, Julia [VerfasserIn]   i
 Rupp, Daniel [VerfasserIn]   i
 Grünvogel, Oliver [VerfasserIn]   i
 Mutz, Pascal [VerfasserIn]   i
 Lasitschka, Felix [VerfasserIn]   i
 Lohmann, Volker [VerfasserIn]   i
 Bartenschlager, Ralf [VerfasserIn]   i
 Cerwenka, Adelheid [VerfasserIn]   i
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

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