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KIR3DS1 directs NK cell-mediated protection against human adenovirus infections.
Jung, Johannes M; Ching, Wilhelm; Baumdick, Martin E; Hofmann-Sieber, Helga; Bosse, Jens B; Koyro, Tobias; Möller, Kimberly J; Wegner, Lucy; Niehrs, Annika; Russu, Kristina; Ohms, Mareike; Zhang, Wenli; Ehrhardt, Anja; Duisters, Kevin; Spierings, Eric; Hölzemer, Angelique; Körner, Christian; Jansen, Suze A; Peine, Sven; Königs, Ingo; Lütgehetmann, Marc; Perez, Daniel; Reinshagen, Konrad; Lindemans, Caroline A; Altfeld, Marcus; Belderbos, Mirjam; Dobner, Thomas; Bunders, Madeleine J.
Afiliación
  • Jung JM; Research Department Virus Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Ching W; Research Department Viral Transformation, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Baumdick ME; Research Department Viral Transformation, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Hofmann-Sieber H; Research Department Virus Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Bosse JB; Research Department Viral Transformation, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Koyro T; Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Möller KJ; Centre for Structural Systems Biology, Hamburg, Germany.
  • Wegner L; Hannover Medical School, Institute of Virology, Hannover, Germany.
  • Niehrs A; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany.
  • Russu K; Research Department Virus Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Ohms M; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Zhang W; Research Department Virus Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Ehrhardt A; Research Department Virus Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Duisters K; Research Department Virus Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Spierings E; Research Department Virus Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Hölzemer A; Research Department Virus Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Körner C; Faculty of Health, Centre for Biomedical Education and Research (ZBAF), School of Human Medicine, Institute of Virology and Microbiology, Witten/Herdecke University, Witten, Germany.
  • Jansen SA; Faculty of Health, Centre for Biomedical Education and Research (ZBAF), School of Human Medicine, Institute of Virology and Microbiology, Witten/Herdecke University, Witten, Germany.
  • Peine S; Mathematical Institute, Leiden University, Leiden, Netherlands.
  • Königs I; Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
  • Lütgehetmann M; Research Department Virus Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Perez D; I. Department of Internal Medicine, Division of Infectious Diseases, University Medical Center Eppendorf, Hamburg, Germany.
  • Reinshagen K; German Center for Infection Research (DZIF), Site Hamburg-Lübeck-Borstel-Riems, Germany.
  • Lindemans CA; Research Department Virus Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Altfeld M; Wilhelmina Children's Hospital/Department of Pediatrics, University Medical Center Utrecht, University Utrecht, Utrecht, Netherlands.
  • Belderbos M; Pediatric Blood and Marrow Transplantation Program, Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands.
  • Dobner T; Regenerative Medicine Center, University Utrecht, Utrecht, Netherlands.
  • Bunders MJ; Institute for Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Sci Immunol ; 6(63): eabe2942, 2021 Sep 17.
Article en En | MEDLINE | ID: mdl-34533978
Human adenoviruses (HAdVs) are a major cause for disease in children, in particular after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Currently, effective therapies for HAdV infections in immunocompromised hosts are lacking. To decipher immune recognition of HAdV infection and determine new targets for immune-mediated control, we used an HAdV infection 3D organoid system, based on primary human intestinal epithelial cells. HLA-F, the functional ligand for the activating NK cell receptor KIR3DS1, was strongly up-regulated and enabled enhanced killing of HAdV5-infected cells in organoids by KIR3DS1+ NK cells. In contrast, HLA-A and HLA-B were significantly down-regulated in HAdV5-infected organoids in response to adenoviral E3/glycoprotein19K, consistent with evasion from CD8+ T cells. Immunogenetic analyses in a pediatric allo-HSCT cohort showed a reduced risk to develop severe HAdV disease and faster clearance of HAdV viremia in children receiving KIR3DS1+/HLA-Bw4+ donor cells compared with children receiving non­KIR3DS1+/HLA-Bw4+ cells. These findings identify the KIR3DS1/HLA-F axis as a new target for immunotherapeutic strategies against severe HAdV disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Asesinas Naturales / Infecciones por Adenovirus Humanos / Receptores KIR3DS1 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Immunol Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Asesinas Naturales / Infecciones por Adenovirus Humanos / Receptores KIR3DS1 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Immunol Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos