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Innate Cytokine Induced Early Release of IFNγ and CC Chemokines from Hypoxic Human NK Cells Is Independent of Glucose

Department of Anesthesiology and Surgical Intensive Care Medicine, Institute for Innate Immunoscience (MI3), University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
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Cells 2020, 9(3), 734; https://doi.org/10.3390/cells9030734
Received: 5 February 2020 / Revised: 13 March 2020 / Accepted: 14 March 2020 / Published: 17 March 2020
(This article belongs to the Section Cellular Immunology)
Natural killer (NK) cells are among the first innate immune cells to arrive at sites of tissue inflammation and regulate the immune response to infection and tumors by the release of cytokines including interferon (IFN)γ. In vitro exposure to the innate cytokines interleukin 15 (IL-15) and IL-12/IL-18 enhances NK cell IFNγ production which, beyond 16 h of culture, was shown to depend on metabolic switching to glycolysis. NK effector responses are, however, rapid by comparison. Therefore, we sought to evaluate the importance of glycolysis for shorter-term IFNγ production, considering glucose deprivation and hypoxia as adverse tissue inflammation associated conditions. Treatments with IL-15 for 6 and 16 h were equally effective in priming early IFNγ production in human NK cells in response to secondary IL-12/IL-18 stimulation. Short-term priming was not associated with glycolytic switching but induced the release of IFNγ and, additionally, CCL3, CCL4 and CCL5 from both normoxic and hypoxic NK cells in an equally efficient and, unexpectedly, glucose independent manner. We conclude that release of IFNγ and CC chemokines in the early innate immune response is a metabolically autonomous NK effector program. View Full-Text
Keywords: glycolysis; hypoxia; inflammation; innate immunity; interferon γ; interleukin 15; natural killer cells; priming glycolysis; hypoxia; inflammation; innate immunity; interferon γ; interleukin 15; natural killer cells; priming
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Velásquez, S.Y.; Himmelhan, B.S.; Kassner, N.; Coulibaly, A.; Schulte, J.; Brohm, K.; Lindner, H.A. Innate Cytokine Induced Early Release of IFNγ and CC Chemokines from Hypoxic Human NK Cells Is Independent of Glucose. Cells 2020, 9, 734.

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