Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation
(2021) Science advances — Vol. 7, n° 19, p. eabf0466 (2021)
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- Authors
Virga, Federico 
Stijlemans, Benoit Henze, Anne-Theres Mazzone, Massimiliano
- Abstract
- 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.
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Virga, F., Cappellesso, F., Stijlemans, B., Henze, A.-T., Trotta, R., Van Audenaerde, J., Mirchandani, A. S., Sanchez-Garcia, M. A., Vandewalle, J., Orso, F., Riera-Domingo, C., Griffa, A., Ivan, C., Smits, E., Laoui, D., Martelli, F., Langouche, L., Van den Berghe, G., Feron, O., et al. (2021). Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation. Science advances, 7(19), eabf0466. https://doi.org/10.1126/sciadv.abf0466 (Original work published 2021)