Abstract
BackgroundProbiotics species appear to differentially regulate the intestinal immune response. Moreover, we have shown that different immune-modulatory abilities can be found among probiotic strains belonging to the same species. In this study, we further addressed this issue while studying L. gasseri, a species that induces relevant immune activities in human patients.ResultsWe determined the ability of two strains of L. gasseri, OLL2809 and L13-Ia, to alter cell surface antigen expression, cytokine production and nuclear erythroid 2-related factor 2 (Nrf2)-mediated cytoprotection in murine bone marrow-derived dendritic cells (DCs) and MODE-K cells, which represent an enterocyte model. Differential effects of L. gasseri strains were observed on the expression of surface markers in mature DCs; nevertheless, both strains dramatically induced production of IL-12, TNF-α and IL-10. Distinctive responses to OLL2809 and L13-Ia were also shown in MODE-K cells by analyzing the expression of MHC II molecules and the secretion of IL-6; however, both L. gasseri strains raised intracellular glutathione. Treatment of immature DCs with culture medium from MODE-K monolayers improved cytoprotection and modified the process of DC maturation by down-regulating the expression of co-stimulatory markers and by altering the cytokine profile. Notably, bacteria-conditioned MODE-K cell medium suppressed the expression of the examined cytokines, whereas cytoprotective defenses were significantly enhanced only in DCs exposed to OLL2809-conditioned medium. These effects were essentially mediated by secreted bacterial metabolites.ConclusionsWe have demonstrated that L. gasseri strains possess distinctive abilities to modulate in vitro DCs and enterocytes. In particular, our results highlight the potential of metabolites secreted by L. gasseri to influence enterocyte-DC crosstalk. Regulation of cellular mechanisms of innate immunity by selected probiotic strains may contribute to the beneficial effects of these bacteria in gut homeostasis.
Highlights
Probiotics species appear to differentially regulate the intestinal immune response
Accumulating data suggest that the nuclear erythroid 2 p45-related factor 2 (Nrf2) is a key regulatory transcription factor that induces defense-related genes that protect against the deleterious effects of reactive oxygen species (ROS) and that targeted activation of this transcription factor could represent a therapeutic approach for the treatment of inflammatory diseases [4]
Probiotic properties of L. gasseri OLL2809 and L13-Ia L. gasseri OLL2809 and L13-Ia have been isolated from human intestine and raw bovine milk, respectively, and their properties have previously been reported [22,23]
Summary
Probiotics species appear to differentially regulate the intestinal immune response. We further addressed this issue while studying L. gasseri, a species that induces relevant immune activities in human patients. Many studies have provided evidence that probiotics can effectively modulate the gut immune system in health and disease [1]. Probiotic bacteria influence both the development and regulation of intestinal immune responses and non-immune defenses [2]. Accumulating data suggest that the nuclear erythroid 2 p45-related factor 2 (Nrf2) is a key regulatory transcription factor that induces defense-related genes that protect against the deleterious effects of reactive oxygen species (ROS) and that targeted activation of this transcription factor could represent a therapeutic approach for the treatment of inflammatory diseases [4]. Bacteria-induced ROS generation greatly influences eukaryotic signaling pathways including those inducing Nrf2 [6,7], and improved Nrf2-mediated protection is associated with beneficial effects elicited by probiotic intake [8,9]
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