Codonopsis pilosula polysaccharide attenuates the inflammatory response in macrophages induced by Brucella abortus outer membrane protein 19 via regulating ATP2A1 to modulate cell adhesion and calcium signaling.

Brucellosis is a zoonotic disease caused by Brucella species. Its pathogenesis is closely associated with bacterial evasion of macrophage-mediated killing, induction of a pro-inflammatory cytokine storm, and immune-mediated pathological damage. Accumulating evidence indicates that Codonopsis pilosula polysaccharides (CPPS) inhibit inflammatory signaling, enhance macrophage phagocytosis, and exert immunomodulatory effects across multiple organs. However, the therapeutic potential of CPPS in brucellosis remains largely unexplored. This study aimed to investigate the effects of CPPS on the inflammatory response induced by Brucella outer membrane protein 19 (OMP19). In vivo, CPPS significantly alleviated tissue damage and simultaneously downregulated the expression of high mobility group box 1 protein (HMGB1), E-cadherin, and paxillin. In vitro, CPPS inhibited SYK/FAK/AKT phosphorylation, PKC activation, and WNT-1 signaling pathway transduction. Additionally, CPPS modulated the cytokine profile by downregulating pro-inflammatory cytokines (TNF-α, IL-6) while increasing the level of the anti-inflammatory cytokine IL-10. Furthermore, CPPS decreased the expression levels of E-cadherin and paxillin and reduced the intracellular calcium ion (Ca2+) concentration. ATP2A1 was identified as a key differentially expressed gene through transcriptome sequencing. Knockdown experiments further confirmed that CPPS exerts anti-inflammatory effects by regulating ATP2A1. Collectively, CPPS attenuates the inflammatory response in macrophages induced by OMP19 via regulating ATP2A1 to modulate cell adhesion and calcium signaling.