NK-cell receptors NKp46 and NCR1 control human metapneumovirus infection

Autor: Oded Danziger, Yaron Drori, Ariella Glasner, Batya Isaacson, Ofer Mandelboim, Alexandra Duev-Cohen, Rachel Zamostiano, Rachel Yamin, Michal Mandelboim, Eran Bacharach, Stipan Jonjić, Mohammad Diab, Yotam Bar-On
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Cytotoxicity
Immunologic
0301 basic medicine
HMPV
MHC class I
MICA
NCR1
NCRs
NK cells
NKG2D
NKp46
respiratory infection
viruses
Lymphocyte Activation
Mice
0302 clinical medicine
Antigens
Ly
Immunology and Allergy
Child
Receptor
Lung
Acute respiratory tract infection
Mice
Knockout
Mice
Inbred BALB C
Paramyxoviridae Infections
Respiratory infection
virus diseases
Viral Load
3. Good health
Killer Cells
Natural
Respiratory virus
BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti
Immunology
Biology
03 medical and health sciences
Immune system
Human metapneumovirus
Animals
Humans
Natural Cytotoxicity Triggering Receptor 1
BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences
Infant
biology.organism_classification
Virology
respiratory tract diseases
HEK293 Cells
030104 developmental biology
biology.protein
Metapneumovirus
030215 immunology
Zdroj: European Journal of Immunology
Volume 47
Issue 4
ISSN: 0014-2980
1521-4141
DOI: 10.1002/eji.201646756
Popis: 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.
Databáze: OpenAIRE
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