Hepatitis D infection induces IFN-β-mediated NK cell activation and TRAIL-dependent cytotoxicity

• Verfasst von: Groth, Christopher [VerfasserIn]
• Verfasst von: Maric, Jovana [VerfasserIn]
• Verfasst von: Garcés Lázaro, Irene [VerfasserIn]
• Verfasst von: Hofman, Tomáš [VerfasserIn]
• Verfasst von: Zhang, Zhenfeng [VerfasserIn]
• Verfasst von: Ni, Yi [VerfasserIn]
• Verfasst von: Keller, Franziska [VerfasserIn]
• Verfasst von: Seufert, Isabelle [VerfasserIn]
• Verfasst von: Hofmann, Maike [VerfasserIn]
• Verfasst von: Neumann-Haefelin, Christoph [VerfasserIn]
• Verfasst von: Sticht, Carsten [VerfasserIn]
• Verfasst von: Rippe, Karsten [VerfasserIn]
• Verfasst von: Urban, Stephan [VerfasserIn]
• Verfasst von: Cerwenka, Adelheid [VerfasserIn]
• Titel: Hepatitis D infection induces IFN-β-mediated NK cell activation and TRAIL-dependent cytotoxicity
• Verf.angabe: Christopher Groth, Jovana Maric, Irene Garcés Lázaro, Tomáš Hofman, Zhenfeng Zhang, Yi Ni, Franziska Keller, Isabelle Seufert, Maike Hofmann, Christoph Neumann-Haefelin, Carsten Sticht, Karsten Rippe, Stephan Urban and Adelheid Cerwenka
• E-Jahr: 2023
• Jahr: 08 December 2023
• Umfang: 15 S.
• Fussnoten: Gesehen am 19.03.2024
• Titel Quelle: Enthalten in: Frontiers in immunology
• Ort Quelle: Lausanne : Frontiers Media, 2010
• Jahr Quelle: 2023
• Band/Heft Quelle: 14(2023) vom: Dez., Artikel-ID 1287367, Seite 1-15
• ISSN Quelle: 1664-3224
• DOI: doi:10.3389/fimmu.2023.1287367
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: HBV
• Sach-SW: HDV
• Sach-SW: IFN-beta
• Sach-SW: NK cells
• Sach-SW: TRAIL
• K10plus-PPN: 1883810493
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

<sec><title>Background and aims</title><p>The co-infection of hepatitis B (HBV) patients with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis and thus drastically worsens the course of the disease. Therapy options for HBV/HDV patients are still limited. Here, we investigated the potential of natural killer (NK) cells that are crucial drivers of the innate immune response against viruses to target HDV-infected hepatocytes.</p></sec><sec><title>Methods</title><p>We established <italic>in vitro</italic> co-culture models using HDV-infected hepatoma cell lines and human peripheral blood NK cells. We determined NK cell activation by flow cytometry, transcriptome analysis, bead-based cytokine immunoassays, and NK cell-mediated effects on T cells by flow cytometry. We validated the mechanisms using CRISPR/Cas9-mediated gene deletions. Moreover, we assessed the frequencies and phenotype of NK cells in peripheral blood of HBV and HDV superinfected patients.</p></sec><sec><title>Results</title><p>Upon co-culture with HDV-infected hepatic cell lines, NK cells upregulated activation markers, interferon-stimulated genes (ISGs) including the death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), produced interferon (IFN)-γ and eliminated HDV-infected cells via the TRAIL-TRAIL-R2 axis. We identified IFN-β released by HDV-infected cells as an important enhancer of NK cell activity. In line with our <italic>in vitro</italic> data, we observed activation of peripheral blood NK cells from HBV/HDV co-infected, but not HBV mono-infected patients.</p></sec><sec><title>Conclusion</title><p>Our data demonstrate NK cell activation in HDV infection and their potential to eliminate HDV-infected hepatoma cells via the TRAIL/TRAIL-R2 axis which implies a high relevance of NK cells for the design of novel anti-viral therapies.</p></sec>