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Abstract
Unbalanced immune responses to invading pathogens can be life-threatening. Therefore, understanding the underlying regulatory mechanisms remains crucial. Here, we show a HIF-1α-dependent miR-210 upregulation in monocytes and macrophages upon pathogen interaction. Genetic ablation of miR-210 in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading and lethality. Pharmacologic miR-210 inhibition improved the survival of septic mice, too. Mechanistically, miR-210 induction in activated macrophages supported a switch towards the pro-inflammatory, M1 state by tuning down mitochondria respiration in favor of glycolysis, partly achieved by downmodulating the Iron-Sulfur Cluster assembly enzyme ISCU. In humans, augmented miR-210 levels in circulating monocytes correlated with the incidence of sepsis, while serum levels of monocyte/macrophage-derived miR-210 were associated with sepsis mortality. Altogether our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses paving the way towards miR-210-based therapeutic and diagnostic strategies.
Original language | English |
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Journal | Science Advances |
DOIs | |
Publication status | Published - 7 May 2021 |
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Dive into the research topics of 'Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation'. Together they form a unique fingerprint.Projects
- 1 Finished
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Defining the interplay between hypoxia and metabolic adaptations of the innate immune response.
1/01/18 → 31/12/22
Project: Research