Metabolite alteration has been associated with the pathogenesis of inflammatory bowel disease (IBD), including colitis. Mannose, a natural bioactive monosaccharide that is involved in metabolism and synthesis of glycoproteins, exhibits anti-inflammatory and anti-oxidative activities. We show here that the circulating level of mannose is increased in patients with IBD and mice with experimental colitis. Mannose treatment attenuates intestinal barrier damage in two mouse colitis models, dextran sodium sulfate (DSS)-induced colitis and spontaneous colitis in IL-10-deficient mice. We demonstrate that mannose treatment enhanced lysosomal integrity and limited the release of cathepsin B, preventing mitochondrial dysfunction and myosin light chain kinase (MLCK)-induced tight junction disruption in the context of intestinal epithelial damage. Mannose exerts a synergistic therapeutic effect with mesalamine on mouse colitis. Cumulatively, the results indicate that mannose supplementation may be an optional approach to the treatment of colitis and other diseases associated with intestinal barrier dysfunction.

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Background: Mannan-binding lectin (MBL), a soluble pattern recognition molecule in the innate immune system, is reported to be associated with the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are mainly characterized by immunosuppressive activities involving several inflammatory diseases such as cancer, infection, and arthritis. Some of the factors inducing their apoptosis are known, however, mechanisms have not been identified. The underlying impact of MBL on the MDSCs especially under inflammatory conditions remains unknown. This study was designed to investigate whether MBL affects MDSCs survival during inflammation conditions. Methods: WT and MBL-deficient (MBL) mice were induced on day 0 of the experiment by subcutaneous injection of complete Freund's adjuvant and then injected with incomplete Freund's adjuvant into the knee joint space under general anesthesia on day 14 to induce inflammatory arthritis. The proportions of MDSCs in the spleen and blood and the serum level of the inflammatory cytokines were measured. In vitro study, MDSCs were isolated from the bone marrow of WT and MBL − / − mice and cultured in the presence of interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for 5 days with or without tumor necrosis factor-alpha (TNF-α).Results: After adjuvant treatment, MBL − / − mice had a significantly lower frequency of MDSCs as well as elevated serum inflammatory cytokines levels compared to WT mice. MBL deficiency markedly inhibited the MDSCs frequency from mice bone marrow induced by IL-6 and GM-CSF in the presence of TNF-α in vitro. Mechanistic studies established that MBL inhibited MDSCs apoptosis via down-regulation of TNF-α/tumor necrosis factor-alpha receptor 1 (TNFR1) signaling pathway and subsequent caspase 3-dependent manner. Conclusion: Mannan-binding lectin deficiency inhibits myeloid-derived suppressor cells expansion via modulating TNF-α triggered apoptosis.