Divergent signaling pathways regulate IL-12 production induced by different species of Lactobacilli in human dendritic cells

• Lactobacillus reuteri 5289 inhibits IL-12 production induced by other Lactobacilli.
• IL-12 production induced by Gram− bacteria is also inhibited by Lactobacillus reuteri 5289.
• IL-12 production by L. acidophilus NCFM is mediated by p38 MAP kinase signal.
• IL-12 inhibition by L. reuteri is sustained by a prolonged activation of ERK1/2.

Recent studies have indicated that different strains of Lactobacilli differ in their ability to regulate IL-12 production by dendritic cells (DCs), as some strains are stronger inducer of IL-12 while other are not and can even inhibit IL-12 production stimulated by IL-12-inducer Lactobacilli.In this report we demonstrate that Lactobacillus reuteri 5289, as previously described for other strains of L. reuteri, can inhibit DC production of IL-12 induced by Lactobacilllus acidophilus NCFM. Remarkably, L. reuteri 5289 was able to inhibit IL-12 production induced not only by Lactobacilli, as so far reported, but also by bacteria of different genera, including pathogens.We investigated in human DCs the signal transduction pathways involved in the inhibition of IL-12 production induced by L. reuteri 5289, showing that this potential anti-inflammatory activity, which is also accompanied by an elevated IL-10 production, is associated to a prolonged phosphorilation of ERK1/2 MAP kinase pathway.Improved understanding of the immune regulatory mechanisms exerted by Lactobacilli is crucial for a more precise employment of these commensal bacteria as probiotics in human immune-mediated pathologies, such as allergies or inflammatory bowel diseases.