Macrophage activation by exopolysaccharides from Streptococcus thermophilus fermented milk through TLRs-mediated NF-ΚB and MAPK pathways

Lactic acid bacteria-derived exopolysaccharides are known for stimulating immune responses. In our previous study, a novel exopolysaccharide (EPS-3A) from skimmed milk fermented by the strain Streptococcus thermophilus (ZJUIDS-2-01) was extracted and structurally characterized. The present study aimed to investigate the effects of EPS-3A on macrophage activation and identify the underlying mechanism. EPS-3A was observed to promote TNF-alpha secretion and phagocytic uptake. RNA-seq analysis identified 949 differentially expressed genes (DEGs). GO analysis revealed that the DEGs were mainly enriched in metabolic pathways relating to the immune system. PPI network, KEGG pathway, western blot and functional verification assays indicated that MAPK and NF-kappa B were the key regulators modulating the expressions of the core gene TNF-alpha. Role and function of TLR2 and TLR4 for the recognition of EPS-3A were also determined. In conclusion, EPS-3A activated macrophages through MAPKs and NF-kappa B signaling mediated at least partly via TLR2 and TLR4.

Automated summary

This study found that EPS-3A, a lactic acid bacteria-derived exopolysaccharide, can activate macrophages through the MAPK and NF-kappa B signaling pathways, thereby promoting immune responses. The results also suggest that the recognition of EPS-3A is partially mediated by TLR2 and TLR4 receptors.