Jung, Johannes M., Ching, Wilhelm, Baumdick, Martin E., Hofmann-Sieber, Helga, Bosse, Jens B., Koyro, Tobias, Moeller, Kimberly J., Wegner, Lucy ORCID: 0000-0001-7330-7669, Niehrs, Annika ORCID: 0000-0002-2190-4346, Russu, Kristina ORCID: 0000-0002-1817-9905, Ohms, Mareike, Zhang, Wenli, Ehrhardt, Anja, Duisters, Kevin ORCID: 0000-0001-5136-5550, Spierings, Eric ORCID: 0000-0001-9441-1019, Hoelzemer, Angelique, Koerner, Christian, Jansen, Suze A., Peine, Sven, Koenigs, Ingo, Luetgehetmann, Marc, Perez, Daniel ORCID: 0000-0002-3154-7311, Reinshagen, Konrad, Lindemans, Caroline A., Altfeld, Marcus, Belderbos, Mirjam, Dobner, Thomas and Bunders, Madeleine J. (2021). KIR3DS1 directs NK cell-mediated protection against human adenovirus infections. Sci. Immunol., 6 (63). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 2470-9468

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Abstract

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/glycoprotein 19K, 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 non-KIR3DS1(+)/HLA-Bw4(+) cells. These findings identify the KIR3DS1/HLA-F axis as a new target for immunotherapeutic strategies against severe HAdV disease.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Jung, Johannes M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ching, WilhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baumdick, Martin E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofmann-Sieber, HelgaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bosse, Jens B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koyro, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moeller, Kimberly J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wegner, LucyUNSPECIFIEDorcid.org/0000-0001-7330-7669UNSPECIFIED
Niehrs, AnnikaUNSPECIFIEDorcid.org/0000-0002-2190-4346UNSPECIFIED
Russu, KristinaUNSPECIFIEDorcid.org/0000-0002-1817-9905UNSPECIFIED
Ohms, MareikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, WenliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ehrhardt, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duisters, KevinUNSPECIFIEDorcid.org/0000-0001-5136-5550UNSPECIFIED
Spierings, EricUNSPECIFIEDorcid.org/0000-0001-9441-1019UNSPECIFIED
Hoelzemer, AngeliqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koerner, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jansen, Suze A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peine, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenigs, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luetgehetmann, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perez, DanielUNSPECIFIEDorcid.org/0000-0002-3154-7311UNSPECIFIED
Reinshagen, KonradUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lindemans, Caroline A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altfeld, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belderbos, MirjamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dobner, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bunders, Madeleine J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-600808
DOI: 10.1126/sciimmunol.abe2942
Journal or Publication Title: Sci. Immunol.
Volume: 6
Number: 63
Date: 2021
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 2470-9468
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NATURAL-KILLER-CELLS; IMMUNE RECONSTITUTION; MYELOID MALIGNANCIES; INVASIVE INFECTION; SURFACE EXPRESSION; DOWN-REGULATION; NKG2D LIGANDS; TRANSPLANTATION; PROTEIN; RECOGNITIONMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60080

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