D-mannose suppresses macrophage IL-1β production

Simone Torretta, Alessandra Scagliola, Luisa Ricci, Francesco Mainini, Sabrina Marco, Ivan Cuccovillo, Anna Kajaste-Rudnitski, David Sumpton, Kevin M. Ryan and Simone Cardaci ()
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Simone Torretta: IRCCS San Raffaele Scientific Institute
Alessandra Scagliola: IRCCS San Raffaele Scientific Institute
Luisa Ricci: IRCCS San Raffaele Scientific Institute
Francesco Mainini: IRCCS San Raffaele Scientific Institute
Sabrina Marco: IRCCS San Raffaele Scientific Institute
Ivan Cuccovillo: IRCCS San Raffaele Scientific Institute
Anna Kajaste-Rudnitski: IRCCS San Raffaele Scientific Institute
David Sumpton: CRUK Beatson Institute
Kevin M. Ryan: CRUK Beatson Institute
Simone Cardaci: IRCCS San Raffaele Scientific Institute

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-20164-6

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