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

Author

Listed:
  • Elisabeth Littwitz-Salomon

    (Trinity College Dublin)

  • Diana Moreira

    (Trinity College Dublin)

  • Joe N. Frost

    (University of Oxford)

  • Chloe Choi

    (Trinity College Dublin)

  • Kevin T. Liou

    (Brown University)

  • David K. Ahern

    (University of Oxford)

  • Simon O’Shaughnessy

    (Trinity College Dublin)

  • Bernd Wagner

    (University Hospital Essen)

  • Christine A. Biron

    (Brown University)

  • Hal Drakesmith

    (University of Oxford)

  • Ulf Dittmer

    (University Hospital Essen, University of Duisburg-Essen)

  • David K. Finlay

    (Trinity College Dublin
    Trinity College Dublin)

Abstract

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.

Suggested Citation

  • Elisabeth Littwitz-Salomon & Diana Moreira & Joe N. Frost & Chloe Choi & Kevin T. Liou & David K. Ahern & Simon O’Shaughnessy & Bernd Wagner & Christine A. Biron & Hal Drakesmith & Ulf Dittmer & David, 2021. "Metabolic requirements of NK cells during the acute response against retroviral infection," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25715-z
    DOI: 10.1038/s41467-021-25715-z
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