IL-1 protects from fatal systemic candidiasis in mice by inhibiting oxidative phosphorylation and hypoxia
(2025) Nature Communications — Vol. 16, n° 1, p. 2626 (2025)
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- Authors
Horn, Sofia 
Berest, Ivan Kopf, Manfred
- Abstract
- Invasive C. albicans infections result in high mortality rates. While IL-1 is important to combat C. albicans infections, the underlying mechanisms remain unclear. Using global and conditional Il1r1 knockouts in mice, here we show that IL-1R signaling in non-hematopoietic cells in the kidney and brain is crucial for a protective response. In the kidney, endothelial IL-1R contributes to fungal clearance independent of neutrophil recruitment, while IL-1R in hematopoietic cells is dispensable. IL-1R signaling indirectly recruits neutrophils and monocytes in the brain by regulating chemokines and adhesion molecules. Single-nucleus-RNA-sequencing data implicates excessive metabolic activity and oxidative phosphorylation across all cell types in the kidney of Il1r1-deficient mice within a few hours upon infection, with associated, localized hypoxia at infection foci. Lastly, we find that hypoxia promotes fungal growth and pathogenicity. In summary, our results show that IL-1R-signaling in non-hematopoietic cells is required to prevent fatal candidiasis by inhibiting a metabolic shift, including excessive oxidative phosphorylation and hypoxia.
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Citations
Horn, S., Schmid, M., Berest, I., Piattini, F., Zhang, J., de Bock, K., Devuyst, O., Nlandu Khodo, S., Kisielow, J., & Kopf, M. (2025). IL-1 protects from fatal systemic candidiasis in mice by inhibiting oxidative phosphorylation and hypoxia. Nature Communications, 16(1), 2626. https://doi.org/10.1038/s41467-025-57797-4 (Original work published 2025)