title: Lactobacillus acidophilus induces virus immune defence genes in murine dendritic cells by a Toll-like receptor-2-dependent mechanism.
abstract: 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.
authors.affiliation: Faculty of Life Sciences, Department of Basic Sciences and Environment, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Weiss
authors.forename: Simon
authors.initials: S
authors.lastname: Rasmussen
authors.forename: Louise Hjerrild
authors.initials: LH
authors.lastname: Zeuthen
authors.forename: Birgit Nøhr
authors.initials: BN
authors.lastname: Nielsen
authors.forename: Hanne
authors.initials: H
authors.lastname: Jarmer
authors.forename: Lene
authors.initials: L
authors.lastname: Jespersen
authors.forename: Hanne
authors.initials: H
authors.lastname: Frøkiaer
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002966:Clathrin / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007779:Lactobacillus acidophilus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D011070:Poly I-C / Q000494:pharmacology; D019936:Probiotics / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051196:Toll-Like Receptor 3 / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D000906:Antibodies; D002966:Clathrin; D016207:Cytokines; C519703:TLR3 protein, mouse; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D018664:Interleukin-12; D016899:Interferon-beta; D011070:Poly I-C