Lactobacillus fermentum attenuates the proinflammatory effect of Yersinia enterocolitica on human epithelial cells

Background: Lactobacilli represent a major component of the human microbiota. In this study we investigated whether and how Lactobacillus fermentum inhibits the proinflammatory responses of human epithelial cells on Yersinia enterocolitica infection. Methods: Human epithelial cells were exposed to Y. enterocolitica pYV(-) or L. fermentum or to both strains, combinations of heat-killed L. fermentum or supernatant of L. fermentum cultures and Y enterocolitica. The modulation of Y. enterocolitica induced IL-8 levels in the Culture supernatants was determined and activation of Rac, p38. and NF-kappa B was investigated. Results: Exposure of human epithelial cells to L. fermentum does not induce NF-kappa B activation and subsequent IL-8 secretion in HeLa cells, whereas Y enterocolitica induces NF-kappa B activation and high levels of IL-8. Viable L. fermentum, supernatant of L. fermentum cultures, but not heat-killed L. fermentum, inhibited IL-8 secretion of HeLa cells triggered by Y. enterocolitica. Lactobacillus fermentum-exposed HeLa cells showed decreased Rac, p38, and NF-kappa B activation after Y. enterocolitica infection. Treatment of L. fermentum supernatants with phospholipase C abolished the inhibitory effect, indicating that a secreted phospholipid mediates the antiinflammatory properties of L. fermentum. Adhesion to or invasion of Y. enterocolitica into epithelial cells was not altered by coincubation with L. fermentum. Conclusion: Our results lead to the conclusion that L. fermentum inhibits the Y. enterocolitica-induced IL-8 production by a possibly secreted phospholipid of < 10 kDa molecular weight. These data suggest that L. fermentum may have probiotic properties modulating intestinal inflammatory responses and might offer new therapeutic strategies in the treatment of intestinal inflammatory diseases.