Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function
| Autor: | Colleen M. Lau, Paolo Giovanelli, Sam Sheppard, Joseph C. Sun, Hyunu Kim, Sara Violante, Endi K. Santosa, Ming Li, Justin R. Cross |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Muromegalovirus Lactate dehydrogenase A CD8-Positive T-Lymphocytes General Biochemistry Genetics and Molecular Biology Article Natural killer cell 03 medical and health sciences 0302 clinical medicine Neoplasms medicine Cytotoxic T cell Animals Homeostasis Glycolysis education Cytotoxicity Cell Proliferation education.field_of_study Chemistry Aerobiosis Cell biology Clone Cells Up-Regulation Killer Cells Natural Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Anaerobic glycolysis Cytomegalovirus Infections Cytokine secretion Lactate Dehydrogenase 5 030217 neurology & neurosurgery CD8 |
| Zdroj: | Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Natural killer (NK) cells are cytotoxic lymphocytes capable of rapid cytotoxicity, cytokine secretion, and clonal expansion. To sustain such energetically demanding processes, NK cells must increase their metabolic capacity upon activation. However, little is known about the metabolic requirements specific to NK cells in vivo. To gain greater insight, we investigated the role of aerobic glycolysis in NK cell function and demonstrate that their glycolytic rate increases rapidly following viral infection and inflammation, prior to that of CD8+ T cells. NK cell-specific deletion of lactate dehydrogenase A (LDHA) reveals that activated NK cells rely on this enzyme for both effector function and clonal proliferation, with the latter being shared with T cells. As a result, LDHA-deficient NK cells are defective in their anti-viral and anti-tumor protection. These findings suggest that aerobic glycolysis is a hallmark of NK cell activation that is key to their function. In brief Sheppard et al. demonstrate that lactate dehydrogenase A (LDHA)-mediated aerobic glycolysis is a hallmark of NK cell activation. LDHA-deficient NK cells, which are unable to perform aerobic glycolysis, are defective in their anti-viral and anti-tumor protection. Graphical abstract |
| Databáze: | OpenAIRE |
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