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Metabolic requirements of NK cells during the acute response against retroviral infection

GND
1099304962
ORCID
0000-0002-6513-0573
LSF
61654
Affiliation
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
Littwitz-Salomon, Elisabeth;
Affiliation
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
Moreira, Diana;
GND
1311641262
ORCID
0000-0002-5946-6062
Affiliation
MRC Human Immunology Unit, MRC Weatherall, Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
Frost, Joe N.;
Affiliation
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
Choi, Chloe;
ORCID
0000-0002-2438-9749
Affiliation
Department of Molecular Microbiology and Immunology, Brown University, Providence, USA
Liou, Kevin T.;
ORCID
0000-0002-7006-7396
Affiliation
MRC Human Immunology Unit, MRC Weatherall, Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
Ahern, David K.;
Affiliation
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
O’Shaughnessy, Simon;
GND
1113794658
ORCID
0000-0003-0877-6906
Affiliation
Department of Clinical Chemistry, University Hospital Essen, Essen, Germany
Wagner, Bernd;
GND
1119457920
ORCID
0000-0001-5117-5052
Affiliation
Department of Molecular Microbiology and Immunology, Brown University, Providence, USA
Biron, Christine A.;
GND
1245465503
ORCID
0000-0002-8503-6103
Affiliation
MRC Human Immunology Unit, MRC Weatherall, Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
Drakesmith, Hal;
GND
1201144469
LSF
47363
Affiliation
Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Dittmer, Ulf;
ORCID
0000-0003-2716-6679
Affiliation
School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
Finlay, David K.
Natural killer (NK) cells are important early responders against viral infections. Changes in metabolism are crucial to fuel NK cell responses, and altered metabolism is linked to NK cell dysfunction in obesity and cancer. However, very little is known about the metabolic requirements of NK cells during acute retroviral infection and their importance for antiviral immunity. Here, using the Friend retrovirus mouse model, we show that following infection NK cells increase nutrient uptake, including amino acids and iron, and reprogram their metabolic machinery by increasing glycolysis and mitochondrial metabolism. Specific deletion of the amino acid transporter Slc7a5 has only discrete effects on NK cells, but iron deficiency profoundly impaires NK cell antiviral functions, leading to increased viral loads. Our study thus shows the requirement of nutrients and metabolism for the antiviral activity of NK cells, and has important implications for viral infections associated with altered iron levels such as HIV and SARS-CoV-2.

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Date Issued:
10.09.2021
URN:
urn:nbn:de:hbz:465-20240905-105057-6
DOI:
10.1038/s41467-021-25715-z
Language:
English
Type of Resource:
Text
Keywords:
Antimicrobial responses; Infection; Innate lymphoid cells; Signal transduction
Collection:
E-Publications
Subject categories of the Deutsche Nationalbibliografie:
610 Medical sciences Medicine
Hosting institution:
Faculty of Medicine, Essen University Hospital, Institute of Virology
Hosting institution:
Scientific institutes, Center of Medical Biotechnology (ZMB)
funding:

The publication of this article was supported by the Publication Fund of the University of Duisburg-Essen.

E.L.-S. is supported by a grant from the German Research Foundation (DFG) LI 3282/1-1. The DKFlab is supported by funding from the European research council (ERC-CoG 770769) and Science Foundation Ireland (18/ERCS/6005). C.C. is supported by an Irish Research Council Government of Ireland Postgraduate Scholarship (GOIPG/2018/2700). The Drakesmith lab is supported by the UK Medical Research Council.

Open Access funding enabled and organized by Projekt DEAL.

Info on primary publication:

Littwitz-Salomon, E., Moreira, D., Frost, J.N. et al. Metabolic requirements of NK cells during the acute response against retroviral infection. Nat Commun 12, 5376 (2021). https://doi.org/10.1038/s41467-021-25715-z

Published 10 September 2021

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