HIF1 α 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-1 α (HIF-1α) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infectionin vivo. HIF-1 α -deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF-1α KO NK cells however, their numbers were significantly reduced. Loss of HIF-1 α did not affect NK cell proliferation duringin vivo infection andin vitro cytokine stimulation. Instead, we found HIF-1 α -deficient NK cells showed increased expression of the pro-apoptotic protein Bim and glucose metabolism was impaired during cytokine stimulationin vitro. Similarly, during MCMV infection HIF-1 α -deficient NK cells upregulated Bim and had increased caspase activity. Thus, NK cells require HIF-1α-dependent metabolic functions to repress Bim expression and sustain cell numbers for an optimal virus response.
Source: eLife - Category: Biomedical Science Tags: Immunology and Inflammation Source Type: research