HIF1α is required for NK cell metabolic adaptation during virus infection.

Autor:	Victorino F; Rheumatology Division, Washington University School of Medicine, St. Louis, United States., Bigley TM; Rheumatology Division, Washington University School of Medicine, St. Louis, United States., Park E; Rheumatology Division, Washington University School of Medicine, St. Louis, United States., Yao CH; Department of Chemistry, Department of Medicine, Washington University, St. Louis, United States., Benoit J; Department of Biomedical Research, Center for Genes, Environment and Health, National Jewish Health, Denver, United States., Yang LP; Rheumatology Division, Washington University School of Medicine, St. Louis, United States., Piersma SJ; Rheumatology Division, Washington University School of Medicine, St. Louis, United States., Lauron EJ; Rheumatology Division, Washington University School of Medicine, St. Louis, United States., Davidson RM; Department of Biomedical Research, Center for Genes, Environment and Health, National Jewish Health, Denver, United States., Patti GJ; Department of Chemistry, Department of Medicine, Washington University, St. Louis, United States., Yokoyama WM; Rheumatology Division, Washington University School of Medicine, St. Louis, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Aug 16; Vol. 10. Date of Electronic Publication: 2021 Aug 16.
DOI:	10.7554/eLife.68484
Abstrakt:	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. Competing Interests: FV, TB, EP, CY, JB, LY, SP, EL, RD, GP, WY none (© 2021, Victorino et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu