Browsing by Author "Griffa, Alberto"

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    Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation
    (American Association for the Advancement of Science, 2021-05-07) Virga, Federico; Cappellesso, Federica; Stijlemans, Benoit; Henze, Anne-Theres; Trotta, Rosa; Van Audenaerde, Jonas; Mirchandani, Ananda S.; Sanchez-Garcia, Manuel A.; Vandewalle, Jolien; Orso, Francesca; Riera-Domingo, Carla; Griffa, Alberto; Ivan, Cristina; Smits, Evelien; Laoui, Damya; Martelli, Fabio; Langouche, Lies; Van den Berghe, Greet; Feron, Olivier; Ghesquière, Bart; Prenen, Hans; Libert, Claude; Walmsley, Sarah R.; Corbet, Cyril; Van Ginderachter, Jo A.; Ivan, Mircea; Taverna, Daniela; Mazzone, Massimiliano; Medicine, School of Medicine
    Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α-dependent microRNA (miR)-210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout 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. Similarly, pharmacologic miR-210 inhibition improved the survival of septic mice. Mechanistically, miR-210 induction in activated macrophages supported a switch toward a proinflammatory state by lessening 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. Together, our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses, suggesting miR-210-based therapeutic and diagnostic strategies.