D-mannose suppresses macrophage IL-1β production

Area of Science:

• Immunology
• Metabolic pathways
• Cellular biology

Background:

• D-mannose, a less common blood monosaccharide, inhibits tumor growth and promotes regulatory T cell differentiation.
• The impact of D-mannose metabolism on non-proliferative cells, like inflammatory macrophages, remains largely unexplored.

Purpose of the Study:

• To investigate the effects of D-mannose on macrophage activation and inflammatory responses.
• To elucidate the underlying metabolic mechanisms by which D-mannose influences macrophage function.

Main Methods:

• Assessed D-mannose effects on lipopolysaccharide (LPS)-induced macrophage activation in vitro.
• Administered D-mannose in mouse models of LPS-induced endotoxemia and DSS-induced colitis.
• Analyzed intracellular mannose-6-phosphate levels, glucose metabolism, and succinate-mediated HIF-1α activation.

Main Results:

• D-mannose suppressed LPS-induced macrophage activation, significantly reducing Interleukin-1 beta (IL-1β) production.
• In vivo, D-mannose administration improved survival in endotoxemia and reduced disease progression in colitis.
• Phosphomannose isomerase activity mediated the suppression by increasing mannose-6-phosphate, impairing glucose metabolism and subsequently reducing IL-1β expression.

Conclusions:

• D-mannose effectively suppresses inflammatory macrophage activation through a specific metabolic pathway involving mannose-6-phosphate and glucose metabolism.
• The study reveals a novel mechanism of metabolic hijacking in macrophage activation.
• D-mannose demonstrates potential as a safe and effective therapeutic agent for managing inflammatory diseases.