Hif1α is required for nk cell metabolic adaptation during virus infection

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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-depen-dent metabolic functions to repress Bim expression and sustain cell numbers for an optimal virus response.

Original languageEnglish
Article numbere68484
JournaleLife
Volume10
DOIs
StatePublished - Aug 2021

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