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Metabolic requirements of NK cells during the acute response against retroviral infection
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Metabolic requirements of NK cells during the acute response against retroviral infection
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Journal Article
Metabolic requirements of NK cells during the acute response against retroviral infection
2021
Overview
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.
Metabolic alterations control the fate and function of immune cells in response to infections, but the function of NK cell metabolism in the context of acute viral infections is unclear. Here the authors show that acute NK cell responses to Friend retrovirus involve increased glycolysis and mitochondrial metabolism and require amino acid transport as well as iron sufficiency.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 45/77
/ 64/60
/ Animals
/ COVID-19
/ HIV
/ Human immunodeficiency virus
/ Humanities and Social Sciences
/ Iron
/ Killer Cells, Natural - immunology
/ Killer Cells, Natural - metabolism
/ Large Neutral Amino Acid-Transporter 1 - genetics
/ Large Neutral Amino Acid-Transporter 1 - metabolism
/ Mice
/ Retroviridae Infections - immunology
/ Retroviridae Infections - virology
/ Science
