Exopolysaccharides From Lactobacillus delbrueckii subsp. bulgaricus OLL1073R‐1 Enhance Macrophage Bactericidal Activity Through IL‐12‐Dependent Macrophage–NK Cell Crosstalk

Abstract

ABSTRACT Exopolysaccharides (EPS) produced by Lactobacillus delbrueckii subsp. bulgaricus OLL1073R‐1 have been reported to exert immunomodulatory effects, primarily in antiviral responses; however, their role in antibacterial host defense remains unclear. Here, we investigated whether EPS enhance macrophage‐mediated killing of Streptococcus pyogenes , a facultative intracellular pathogen, using an in vitro co‐culture system with NK‐like cells. EPS alone did not enhance the intracellular bactericidal activity of macrophages. In contrast, EPS significantly increased bacterial killing when macrophages were co‐cultured with NK‐like cells. Mechanistically, EPS induced interleukin (IL)−12 expression in macrophages, while interferon (IFN)‐γ production was not detected when macrophages or NK‐like cells were cultured separately, but was significantly induced in the co‐culture system. Neutralization of IL‐12 or IFN‐γ significantly abrogated the EPS‐mediated enhancement of bactericidal activity, indicating that both cytokines are required for this effect. These findings support a model in which EPS stimulate macrophages to produce IL‐12, leading to NK cell activation and subsequent IFN‐γ–dependent enhancement of macrophage bactericidal function. Our results reveal a previously uncharacterized role of probiotic‐derived EPS in promoting antibacterial immunity through macrophage–NK cell crosstalk.