Insights into oral lentinan immunomodulation: Dectin-1-mediated lymphatic transport from Peyer's patch M cells to mononuclear phagocytes

Lentinan (LNT), a natural polysaccharide, has been reported to exhibit immunomodulatory effects in the intestine after oral administration. Herein, we aimed to investigate the lymphatic transport of LNT in Peyer's patches (PPs) by traceable fluorescent labeling and to explore whether/how LNT contacts related immune cells. Near-infrared imaging confirmed the absorption of LNT in the small intestinal segment and its accumulation within PPs after oral administration. Subsequently, tissue imaging confirmed that M cells are the main cells responsible for transporting LNT to PPs, and an M cell model was established to explore the involvement of Dectin-1 in the absorption process. Systematic in vitro and in vivo studies revealed that the Dectin-1 further mediates the uptake of LNT by mononuclear phagocytes in PPs. Moreover, LNT can promote the proliferation and differentiation of mononuclear phagocytes, thereby activating immune responses. In summary, this study elucidates the pharmacokinetic mechanisms by which LNT exerts oral immunomodulatory effects, providing a theoretical basis for the development and application of other polysaccharides.