Protective effect of Lactococcus lactis NZ9000 secreting Bcl2 against Trichinella spiralis infection in mice.

Abstract

BACKGROUND: Trichinellosis, a globally distributed zoonosis, threatens both human health and livestock productivity. The limited efficacy of existing anthelmintics underscores the need for innovative strategies to control Trichinella spiralis infection. RESULTS: A recombinant food-grade Lactococcus lactis strain (NZ-Bcl2) was engineered to secrete the anti-apoptotic protein Bcl2 by fusing the Bcl2 gene to the Usp45 signal peptide. Western blotting confirmed successful expression and secretion. NZ-Bcl2 strains exhibited stable growth, maintained plasmid inheritance over 24 generations without antibiotic pressure, and persisted in the murine intestine for at least seven days. In low-dose infections (150 larvae/mouse), oral administration of NZ-Bcl2 significantly reduced muscle larval burden, mitigated intestinal damage, and alleviated mesenteric lymph node enlargement. These protective effects were associated with downregulation of pro-inflammatory cytokines (IL-1β, TNF-α), upregulation of anti-inflammatory cytokines (IL-10, TGF-β), and increased expression of intestinal barrier markers (claudin-3, MUC-1). Under high-dose challenge (600 larvae/mouse), the protective effects were attenuated. CONCLUSION: Recombinant L. lactis secreting Bcl2 confers partial protection against T. spiralis by enhancing mucosal barrier function and modulating host immunity. These findings highlight the potential of engineered probiotics as a novel platform for antiparasitic intervention, offering translational relevance for food safety and zoonotic disease control.