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

Immunology. 2010 Oct;131(2):268-81. doi: 10.1111/j.1365-2567.2010.03301.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology
  • Clathrin / metabolism
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Endocytosis / drug effects
  • Endocytosis / immunology
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Immunity, Innate / genetics*
  • Immunity, Innate / immunology
  • Interferon-beta / genetics
  • Interferon-beta / immunology
  • Interferon-beta / metabolism
  • Interleukin-12 / metabolism
  • Lactobacillus acidophilus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Poly I-C / pharmacology
  • Probiotics / pharmacology
  • Toll-Like Receptor 2 / genetics*
  • Toll-Like Receptor 3 / genetics
  • Up-Regulation / genetics
  • Up-Regulation / immunology

Substances

  • Antibodies
  • Clathrin
  • Cytokines
  • TLR3 protein, mouse
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 3
  • Interleukin-12
  • Interferon-beta
  • Poly I-C