Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Int Immunopharmacol. 2022 Jul;108:108875. doi: 10.1016/j.intimp.2022.108875. Epub 2022 May 21.
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-α 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-κB were the key regulators modulating the expressions of the core gene TNF-α. 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-κB signaling mediated at least partly via TLR2 and TLR4.
乳酸菌衍生的胞外多糖以刺激免疫反应而闻名。在我们之前的研究中，从嗜热链球菌（ZJUIDS-2-01）发酵的脱脂乳中提取并结构表征了一种新型胞外多糖（EPS-3A）。本研究旨在探讨 EPS-3A 对巨噬细胞激活的影响，并确定其潜在机制。结果表明，EPS-3A 可促进 TNF-α 的分泌和吞噬作用。RNA-seq 分析鉴定出 949 个差异表达基因（DEGs）。GO 分析表明，DEGs 主要富集在与免疫系统相关的代谢途径中。PPI 网络、KEGG 通路、western blot 和功能验证实验表明，MAPK 和 NF-κB 是调节核心基因 TNF-α表达的关键调节剂。还确定了 TLR2 和 TLR4 在识别 EPS-3A 中的作用和功能。总之，EPS-3A 通过 MAPK 和 NF-κB 信号通路激活巨噬细胞，至少部分通过 TLR2 和 TLR4 介导。
