D-mannose suppresses macrophage IL-1β production

Torretta, S., Scagliola, A., Ricci, L., Mainini, F., Di Marco, S., Cuccovillo, I., Kajaste-Rudnitski, A., Sumpton, D., Ryan, K. M. and Cardaci, S. (2020) D-mannose suppresses macrophage IL-1β production. Nature Communications, 11, 6343. (doi: 10.1038/s41467-020-20164-6) (PMID:33311467) (PMCID:PMC7733482)

Abstract

D-mannose is a monosaccharide approximately a hundred times less abundant than glucose in human blood. Previous studies demonstrated that supraphysiological levels of D-mannose inhibit tumour growth and stimulate regulatory T cell differentiation. It is not known whether D-mannose metabolism affects the function of non-proliferative cells, such as inflammatory macrophages. Here, we show that D-mannose suppresses LPS-induced macrophage activation by impairing IL-1β production. In vivo, mannose administration improves survival in a mouse model of LPS-induced endotoxemia as well as decreases progression in a mouse model of DSS-induced colitis. Phosphomannose isomerase controls response of LPS-activated macrophages to D-mannose, which impairs glucose metabolism by raising intracellular mannose-6-phosphate levels. Such alterations result in the suppression of succinate-mediated HIF-1α activation, imposing a consequent reduction of LPS-induced Il1b expression. Disclosing an unrecognized metabolic hijack of macrophage activation, our study points towards safe D-mannose utilization as an effective intervention against inflammatory conditions.

• Item Type: Articles
• Additional Information: The research leading to these results has received funding from AIRC under Start-Up 2017—ID. 20464 project—P.I. S.C. and by Bando della Ricerca Finalizzata 2018 GR-2018-12365954 to S.C. K.M.R. is supported by Cancer Research UK (A22903 and A17196).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sumpton, Mr David and Ryan, Professor Kevin and Cardaci, Dr Simone
• Authors: Torretta, S., Scagliola, A., Ricci, L., Mainini, F., Di Marco, S., Cuccovillo, I., Kajaste-Rudnitski, A., Sumpton, D., Ryan, K. M., and Cardaci, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Nature Communications 11: 6343
• Publisher Policy: Reproduced under a Creative Commons License