Science immunology · 2021
KIR3DS1 directs NK cell-mediated protection against human adenovirus infections.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.