Lactobacillus acidophilus induces virus immune defence genes in murine dendritic cells by a Toll‐like receptor‐2‐dependent mechanism

Lactobacilli are probiotics that, among other health‐promoting effects, have been ascribed immunostimulating and virus‐preventive properties. Certain Lactobacillus spp. have been shown to possess strong interleukin‐12 (IL‐12) ‐inducing properties. As IL‐12 production depends on the up‐regulation of type I interferons (IFNs), we hypothesized that the strong IL‐12‐inducing capacity of Lactobacillus acidophilus NCFM in murine bone‐marrow‐derived dendritic cells (DCs) is caused by an up‐regulation of IFN‐β, which subsequently induces IL‐12 and the double‐stranded RNA binding Toll‐like receptor‐3 (TLR‐3). The expression of the genes encoding IFN‐β, TLR‐3, IL‐12 and IL‐10 in DCs upon stimulation with L. acidophilus NCFM was determined. Lactobacillus acidophilus NCFM induced a much stronger expression of Ifn‐β, Il‐12 and Il‐10 compared with the synthetic double‐stranded RNA ligand Poly I:C, whereas the levels of expressed Tlr‐3 were similar. Whole genome microarray gene expression analysis revealed that other genes related to viral defence were significantly up‐regulated and among the strongest induced genes in DCs stimulated with L. acidophilus NCFM. The ability to induce IFN‐β was also detected in another L. acidophilus strain (X37), but was not a property of other probiotic strains tested, i.e. Bifidobacterium bifidum Z9 and Escherichia coli Nissle 1917. The IFN‐β expression was markedly reduced in TLR‐2−/− DCs, dependent on endocytosis, and the major cause of the induction of Il‐12 and Tlr‐3 in DCs stimulated with L. acidophilus NCFM. Collectively, our results reveal that certain lactobacilli trigger the expression of viral defence genes in DCs in a TLR‐2 manner dependent on IFN‐β.