HIF1α is required for NK cell metabolic adaptation during virus infection

Natural killer (NK) cells are essential for early protection against virus infection and must metabolically adapt to the energy demands of activation. Here, we found upregulation of the metabolic adaptor hypoxia-inducible factor-1α (HIF1α) is a feature of mouse NK cells during murine cytomegalovirus...

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Autores principales:	Francisco Victorino, Tarin M Bigley, Eugene Park, Cong-Hui Yao, Jeanne Benoit, Li-Ping Yang, Sytse J Piersma, Elvin J Lauron, Rebecca M Davidson, Gary J Patti, Wayne M Yokoyama
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	HIF1α NK cells MCMV apoptosis metabolism Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3e3a62a1b135404db887eff1f946aea3
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spelling	oai:doaj.org-article:3e3a62a1b135404db887eff1f946aea32021-11-25T12:30:58ZHIF1α is required for NK cell metabolic adaptation during virus infection10.7554/eLife.684842050-084Xe68484https://doaj.org/article/3e3a62a1b135404db887eff1f946aea32021-08-01T00:00:00Zhttps://elifesciences.org/articles/68484https://doaj.org/toc/2050-084XNatural killer (NK) cells are essential for early protection against virus infection and must metabolically adapt to the energy demands of activation. Here, we found upregulation of the metabolic adaptor hypoxia-inducible factor-1α (HIF1α) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infection in vivo. HIF1α-deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF1αKO NK cells; however, their numbers were significantly reduced. Loss of HIF1α did not affect NK cell proliferation during in vivo infection and in vitro cytokine stimulation. Instead, we found that HIF1α-deficient NK cells showed increased expression of the pro-apoptotic protein Bim and glucose metabolism was impaired during cytokine stimulation in vitro. Similarly, during MCMV infection HIF1α-deficient NK cells upregulated Bim and had increased caspase activity. Thus, NK cells require HIF1α-dependent metabolic functions to repress Bim expression and sustain cell numbers for an optimal virus response.Francisco VictorinoTarin M BigleyEugene ParkCong-Hui YaoJeanne BenoitLi-Ping YangSytse J PiersmaElvin J LauronRebecca M DavidsonGary J PattiWayne M YokoyamaeLife Sciences Publications LtdarticleHIF1αNK cellsMCMVapoptosismetabolismMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIF1α NK cells MCMV apoptosis metabolism Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	HIF1α NK cells MCMV apoptosis metabolism Medicine R Science Q Biology (General) QH301-705.5 Francisco Victorino Tarin M Bigley Eugene Park Cong-Hui Yao Jeanne Benoit Li-Ping Yang Sytse J Piersma Elvin J Lauron Rebecca M Davidson Gary J Patti Wayne M Yokoyama HIF1α is required for NK cell metabolic adaptation during virus infection
description	Natural killer (NK) cells are essential for early protection against virus infection and must metabolically adapt to the energy demands of activation. Here, we found upregulation of the metabolic adaptor hypoxia-inducible factor-1α (HIF1α) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infection in vivo. HIF1α-deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF1αKO NK cells; however, their numbers were significantly reduced. Loss of HIF1α did not affect NK cell proliferation during in vivo infection and in vitro cytokine stimulation. Instead, we found that HIF1α-deficient NK cells showed increased expression of the pro-apoptotic protein Bim and glucose metabolism was impaired during cytokine stimulation in vitro. Similarly, during MCMV infection HIF1α-deficient NK cells upregulated Bim and had increased caspase activity. Thus, NK cells require HIF1α-dependent metabolic functions to repress Bim expression and sustain cell numbers for an optimal virus response.
format	article
author	Francisco Victorino Tarin M Bigley Eugene Park Cong-Hui Yao Jeanne Benoit Li-Ping Yang Sytse J Piersma Elvin J Lauron Rebecca M Davidson Gary J Patti Wayne M Yokoyama
author_facet	Francisco Victorino Tarin M Bigley Eugene Park Cong-Hui Yao Jeanne Benoit Li-Ping Yang Sytse J Piersma Elvin J Lauron Rebecca M Davidson Gary J Patti Wayne M Yokoyama
author_sort	Francisco Victorino
title	HIF1α is required for NK cell metabolic adaptation during virus infection
title_short	HIF1α is required for NK cell metabolic adaptation during virus infection
title_full	HIF1α is required for NK cell metabolic adaptation during virus infection
title_fullStr	HIF1α is required for NK cell metabolic adaptation during virus infection
title_full_unstemmed	HIF1α is required for NK cell metabolic adaptation during virus infection
title_sort	hif1α is required for nk cell metabolic adaptation during virus infection
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/3e3a62a1b135404db887eff1f946aea3
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_version_	1718413491374653440

HIF1α is required for NK cell metabolic adaptation during virus infection

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