Bangia fusco-purpurea polysaccharide exerts immunomodulatory effects through Lactobacillus murinus -mediated macrophage polarization via the MAPK/NF-κB-IL10 signaling axis

Abstract Immunomodulation is the primary biological activity of polysaccharides. We have previously demonstrated that Bangia fusco-purpurea polysaccharide (BFP) can modulate the immune function of immunosuppressed mice and increase the abundance of Lactobacillus murinus. However, the underlying mechanisms remain unclear. In the present study, we aimed to elucidate the L. murinus-mediated immunomodulatory effect of BFP. Co-culture of L. murinus and BFP revealed that BFP promoted the proliferation of L. murinus at the concentrations of 0.5%–2.0%. We established a mouse L. murinus depletion model, in which L. murinus was administered via gavage. Treatment with L. murinus significantly increased macrophage phagocytosis and the levels of immune-related factors in mice, including interleukin (IL)-2, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). These results suggested that L. murinus contributes to the immunomodulatory effect of BFP. Given the important role of macrophages in innate and adaptive immunity, we further confirmed that L. murinus can enhance immune function. Under lipopolysaccharide (LPS)-induced inflammatory conditions, L. murinus stimulated the elevation of IL-10 expression, consequently promoted macrophages polarization toward the anti-inflammatory M2 type, which in turn prevented the overactivation of the inflammatory response and reversed the LPS-induced inflammation. It also maintained the balance between pro- and anti-inflammatory responses, thus playing a role in regulating immune function. Finally, transcriptomic sequencing and pathway validation revealed that L. murinus regulates IL-10 through the macrophage/mitogen-activated protein kinase/nuclear factor-κB (MAPK/NF-κB) signaling axis. Overall, these results suggest that the immunomodulatory mechanism of the BFP may involve L. murinus-induced regulation of IL-10 through the macrophage/MAPK/NF-κB signaling axis.