HIF1α is required for NK cell metabolic adaptation during virus infection

eLife

Jeanne Benoit¹  Rebecca M Davidson¹  Cong-Hui Yao²  Gary Patti²  Wayne M Yokoyama³  Sytse J Piersma³  Francisco Victorino³  Elvin J Lauron³  Liping Yang³  Eugene Park³  Tarin Bigley³ 

[1] Department of Biomedical Research, Center for Genes, Environment and Health, National Jewish Health, Denver, United States;Department of Chemistry, Department of Medicine, Washington University, St. Louis, United States;Rheumatology Division, Washington University School of Medicine, St. Louis, United States;

关键词: HIF1α;    NK cells;    MCMV;    apoptosis;    metabolism;    Mouse;   

DOI  :  10.7554/eLife.68484

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY