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KIR3DS1 directs NK cell-mediated protection against human adenovirus infections

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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.

in: SCI IMMUNOL, Jahrgang 6, Nr. 63, eabe2942, 17.09.2021.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Jung, JM, Ching, W, Baumdick, ME, Hofmann-Sieber, H, Bosse, JB, Koyro, T, Möller, KJ, Wegner, L, Niehrs, A, Russu, K, Ohms, M, Zhang, W, Ehrhardt, A, Duisters, K, Spierings, E, Hölzemer, A, Körner, C, Jansen, SA, Peine, S, Königs, I, Lütgehetmann, M, Perez, D, Reinshagen, K, Lindemans, CA, Altfeld, M, Belderbos, M, Dobner, T & Bunders, MJ 2021, 'KIR3DS1 directs NK cell-mediated protection against human adenovirus infections', SCI IMMUNOL, Jg. 6, Nr. 63, eabe2942. https://doi.org/10.1126/sciimmunol.abe2942

APA

Jung, J. M., Ching, W., Baumdick, M. E., Hofmann-Sieber, H., Bosse, J. B., Koyro, T., Möller, K. J., Wegner, L., Niehrs, A., Russu, K., Ohms, M., Zhang, W., Ehrhardt, A., Duisters, K., Spierings, E., Hölzemer, A., Körner, C., Jansen, S. A., Peine, S., ... Bunders, M. J. (2021). KIR3DS1 directs NK cell-mediated protection against human adenovirus infections. SCI IMMUNOL, 6(63), [eabe2942]. https://doi.org/10.1126/sciimmunol.abe2942

Vancouver

Jung JM, Ching W, Baumdick ME, Hofmann-Sieber H, Bosse JB, Koyro T et al. KIR3DS1 directs NK cell-mediated protection against human adenovirus infections. SCI IMMUNOL. 2021 Sep 17;6(63). eabe2942. https://doi.org/10.1126/sciimmunol.abe2942

Bibtex

@article{7be35cd665754e7798e4dc3e7767afc7,
title = "KIR3DS1 directs NK cell-mediated protection against human adenovirus infections",
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/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 non–KIR3DS1+/HLA-Bw4+ cells. These findings identify the KIR3DS1/HLA-F axis as a new target for immunotherapeutic strategies against severe HAdV disease.",
author = "Jung, {Johannes M} and Wilhelm Ching and Baumdick, {Martin E} and Helga Hofmann-Sieber and Bosse, {Jens B} and Tobias Koyro and M{\"o}ller, {Kimberly J} and Lucy Wegner and Annika Niehrs and Kristina Russu and Mareike Ohms and Wenli Zhang and Anja Ehrhardt and Kevin Duisters and Eric Spierings and Angelique H{\"o}lzemer and Christian K{\"o}rner and Jansen, {Suze A} and Sven Peine and Ingo K{\"o}nigs and Marc L{\"u}tgehetmann and Daniel Perez and Konrad Reinshagen and Lindemans, {Caroline A} and Marcus Altfeld and Mirjam Belderbos and Thomas Dobner and Bunders, {Madeleine J}",
year = "2021",
month = sep,
day = "17",
doi = "10.1126/sciimmunol.abe2942",
language = "English",
volume = "6",
journal = "SCI IMMUNOL",
issn = "2470-9468",
publisher = "American Association for the Advancement of Science",
number = "63",

}

RIS

TY - JOUR

T1 - KIR3DS1 directs NK cell-mediated protection against human adenovirus infections

AU - Jung, Johannes M

AU - Ching, Wilhelm

AU - Baumdick, Martin E

AU - Hofmann-Sieber, Helga

AU - Bosse, Jens B

AU - Koyro, Tobias

AU - Möller, Kimberly J

AU - Wegner, Lucy

AU - Niehrs, Annika

AU - Russu, Kristina

AU - Ohms, Mareike

AU - Zhang, Wenli

AU - Ehrhardt, Anja

AU - Duisters, Kevin

AU - Spierings, Eric

AU - Hölzemer, Angelique

AU - Körner, Christian

AU - Jansen, Suze A

AU - Peine, Sven

AU - Königs, Ingo

AU - Lütgehetmann, Marc

AU - Perez, Daniel

AU - Reinshagen, Konrad

AU - Lindemans, Caroline A

AU - Altfeld, Marcus

AU - Belderbos, Mirjam

AU - Dobner, Thomas

AU - Bunders, Madeleine J

PY - 2021/9/17

Y1 - 2021/9/17

N2 - 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 non–KIR3DS1+/HLA-Bw4+ cells. These findings identify the KIR3DS1/HLA-F axis as a new target for immunotherapeutic strategies against severe HAdV disease.

AB - 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 non–KIR3DS1+/HLA-Bw4+ cells. These findings identify the KIR3DS1/HLA-F axis as a new target for immunotherapeutic strategies against severe HAdV disease.

U2 - 10.1126/sciimmunol.abe2942

DO - 10.1126/sciimmunol.abe2942

M3 - SCORING: Journal article

C2 - 34533978

VL - 6

JO - SCI IMMUNOL

JF - SCI IMMUNOL

SN - 2470-9468

IS - 63

M1 - eabe2942

ER -