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

Wei Xu; Feiwei Cao; Ming Zhao; Xinyu Fu; Siyuan Yin; Yijia Sun; Teresa G Valencak; Daxi Ren

doi:10.1016/j.intimp.2022.108875

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

Int Immunopharmacol. 2022 Jul:108:108875. doi: 10.1016/j.intimp.2022.108875. Epub 2022 May 21.

Authors

Wei Xu¹, Feiwei Cao², Ming Zhao³, Xinyu Fu⁴, Siyuan Yin⁵, Yijia Sun⁶, Teresa G Valencak⁷, Daxi Ren⁸

Affiliations

¹ 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. Electronic address: xuwei88@zju.edu.cn.
² Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: caofeiwei@zju.edu.cn.
³ Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: mingzhao1020@zju.edu.cn.
⁴ Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: xyfu@zju.edu.cn.
⁵ Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: 3190101256@zju.edu.cn.
⁶ Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: 3190101334@zju.edu.cn.
⁷ Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: teresavalencak@zju.edu.cn.
⁸ Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: dxren@zju.edu.cn.

PMID: 35609378
DOI: 10.1016/j.intimp.2022.108875

Abstract

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.

Keywords: Exopolysaccharides; Immunomodulation; MAPK; Macrophage; NF-κB; TLRs.

MeSH terms

Animals
Macrophage Activation*
Milk / metabolism
NF-kappa B / metabolism
Streptococcus thermophilus* / metabolism
Toll-Like Receptor 2 / metabolism
Toll-Like Receptor 4 / genetics
Toll-Like Receptor 4 / metabolism
Tumor Necrosis Factor-alpha / metabolism

Substances

NF-kappa B
Toll-Like Receptor 2
Toll-Like Receptor 4
Tumor Necrosis Factor-alpha