Lactobacilli have been suggested to have a preventative and therapeutic effect on gastritis caused by Helicobacter pylori infection. In this study, we stimulated murine bone marrow derived macrophages with Lactobacillus acidophilus and Helicobacter pylori to identify the cellular and molecular pathways activated upon stimulation with both bacteria. Microarray analysis revealed that H. pylori induces a pro-inflammatory response with a high expression of neutrophil recruiting chemokines (Cxcl3, Cxcl1, Cxcl2 and other genes involved in chemotaxis and production of granulocytes) and cytokines (IL-1beta and IL-1alpha). In contrast, L. acidophilus activates not only a strong pro-inflammatory but also a strong Th1 response characterised by a high expression of IL-12 and IFN-ß and the T-cell recruiting chemokines Cxcl10 and Cxcl11. Unexpectedly, when both bacteria were added in combination, H. pylori was able to completely block the expression of IFN-ß and IL-12 induced by L. acidophilus. Other strongly down-regulated genes are Rgs1/2, Fgd2, and Dock8, all involved in Rho, Rac and Cdc42 GTPase signalling, which are key regulators of the actin cytoskeleton. Two genes were strongly induced upon addition of both bacteria to the macrophages: P2rx2 and Pdxp, both involved in actin cytoskeleton alterations.
We tested two of the main virulence factors of H. pylori: Cag pathogenicity island (cagPAI) and Vacuolating cytotoxin (VacA). The inhibitory capacity of the CagPAI mutant was identical to the WT, however, the VacA mutant was unable to block IFN-β. Phagosomal maturation inhibitors completely abrogated the induction of IFN-β. Confocal microscopy revealed that instead of a quick endosomal release into the cytoplasm, L. acidophilus gets trapped in the endosomal/lysosomal compartments in H. pylori infected macrophages. Our data indicates that H. pylori disrupts intracellular trafficking of L. acidophilus via endocytic alterations and thereby abrogates IFN-β signalling.