Innate Cytokine Induced Early Release of IFNγ and CC Chemokines from Hypoxic Human NK Cells Is Independent of Glucose
Sonia Y. Velásquez,
Bianca S. Himmelhan,
Nina Kassner,
Anna Coulibaly,
Jutta Schulte,
Kathrin Brohm,
Holger A. Lindner
Affiliations
Sonia Y. Velásquez
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
Bianca S. Himmelhan
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
Nina Kassner
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
Anna Coulibaly
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
Jutta Schulte
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
Kathrin Brohm
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
Holger A. Lindner
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
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.
