title: NK-cell receptors NKp46 and NCR1 control human metapneumovirus infection.
abstract: Natural killer (NK) cells are capable of killing various pathogens upon stimulation of activating receptors. Human metapneumovirus (HMPV) is a respiratory virus, which was discovered in 2001 and is responsible for acute respiratory tract infection in infants and children worldwide. HMPV infection is very common, infecting around 70% of all children under the age of five. Under immune suppressive conditions, HMPV infection can be fatal. Not much is known on how NK cells respond to HMPV. In this study, using reporter assays and NK-cell cytotoxicity assays performed with human and mouse NK cells, we demonstrated that the NKp46-activating receptor and its mouse orthologue Ncr1, both members of the natural cytotoxicity receptor (NCR) family, recognized an unknown ligand expressed by HMPV-infected human cells. We demonstrated that MHC class I is upregulated and MICA is downregulated upon HMPV infection. We also characterized mouse NK-cell phenotype in the blood and the lungs of HMPV-infected mice and found that lung NK cells are more activated and expressing NKG2D, CD43, CD27, KLRG1, and CD69 compared to blood NK cells regardless of HMPV infection. Finally, we demonstrated, using Ncr1-deficient mice, that NCR1 plays a critical role in controlling HMPV infection.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, the BioMedical Research Institute Israel-Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Diab
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, the BioMedical Research Institute Israel-Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ariella
authors.initials: A
authors.lastname: Glasner
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, the BioMedical Research Institute Israel-Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Batya
authors.initials: B
authors.lastname: Isaacson
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, the BioMedical Research Institute Israel-Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Yotam
authors.initials: Y
authors.lastname: Bar-On
authors.affiliation: Central Virology Laboratory, Ministry of Health, Public Health Services, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.|Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Drori
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, the BioMedical Research Institute Israel-Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Yamin
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, the BioMedical Research Institute Israel-Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Duev-Cohen
authors.affiliation: Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Danziger
authors.affiliation: Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Zamostiano
authors.affiliation: Central Virology Laboratory, Ministry of Health, Public Health Services, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.|Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Mandelboim
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.|Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjic
authors.affiliation: Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Bacharach
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, the BioMedical Research Institute Israel-Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism*; D002648:Child; D003602:Cytotoxicity, Immunologic; D057809:HEK293 Cells; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D029121:Metapneumovirus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000378:metabolism*; D018184:Paramyxoviridae Infections / Q000276:immunology*; D019562:Viral Load
chemical_list: D000950:Antigens, Ly; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse
keywords: HMPV; MHC class I; MICA; NCR1; NCRs; NK cells; NKG2D; NKp46; respiratory infection