D-mannose blocks S-adenosylmethionine generation to suppress macrophage IL-1β expression.

Authors

Yingyi Chen, Junji Xu, Jingfei Fu, Juan Du, Ziqing Feng, Minfeng Wang, Yi Liu, Yitong Liu

Published in

Frontiers in immunology. Volume 17. Pages 1895029. Epub Aug 21, 2026.

Abstract

Inflammatory stimuli drive metabolic reprogramming in macrophages, supplying energy, reducing equivalents, and methyl donors required for the production of inflammatory mediators such as IL-1β; however, metabolic strategies to regulate this pathway remain unclear. Here, we aimed to define the mechanism by which D-mannose suppresses one-carbon metabolism in inflammatory macrophages and thereby epigenetically restrains inflammatory responses.
Untargeted metabolomics was used to define the global metabolic effects of D-mannose in inflammatory macrophages. 6-phosphogluconate dehydrogenase activity and real-time ATP rate assays were performed to assess nicotinamide adenine dinucleotide phosphate (NADPH) and adenosine triphosphate (ATP) generation. S-adenosylmethionine (SAM) and cytokine levels were measured by enzyme-linked immunosorbent assay, and epigenetic regulation at the Il1b promoter was examined by chromatin immunoprecipitation-qPCR and immunoblotting. A murine full-thickness skin wound model with macrophage depletion was used for in vivo validation.
D-mannose suppressed metabolic flux through glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway, resulting in reduced ATP and NADPH production. This metabolic restriction impaired one-carbon metabolism, decreased SAM abundance, and reduced histone H3 lysine 36 trimethylation enrichment at the Il1b promoter, thereby repressing Il1b transcription. These effects were reversed by exogenous SAM supplementation. Macrophages exhibited a metabolic bottleneck associated with low mannose phosphate isomerase (Mpi) expression. Consistently, Mpi overexpression reversed the D-mannose-induced reductions in ATP and SAM levels, as well as Il1b expression. Topical D-mannose also lowered SAM and IL-1β levels in wound tissues and accelerated wound healing in vivo.
D-mannose suppresses macrophage pro-inflammatory transcription through a one-carbon metabolism-epigenetic axis, supporting its potential as a metabolism-targeted strategy for inflammatory wound repair.

PMID:
42698684
Bibliographic data and abstract were imported from PubMed on 24 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.