title: Dose-dependent immunomodulation of human dendritic cells by the probiotic Lactobacillus rhamnosus Lcr35.
abstract: The response of the immune system to probiotics remains controversial. Some strains modulate the cytokine production of dendritic cells (DCs) in vitro and induce a regulatory response, while others induce conversely a pro-inflammatory response. These strain-dependent effects are thought to be linked to specific interactions between bacteria and pattern recognition receptors. We investigated the effects of a well characterized probiotic strain, Lactobacillus rhamnosus Lcr35, on human monocyte-derived immature DCs, using a wide range of bacterial concentrations (multiplicity of infection, MOI, from 0.01 to 100). DNA microarray and qRT-PCR analysis showed that the probiotic induced a large-scale change in gene expression (nearly 1,700 modulated genes, with 3-fold changes), but only with high doses (MOI, 100). The upregulated genes were mainly involved in immune response and identified a molecular signature of inflammation according to the model of Torri. Flow cytometry analysis also revealed a dose-dependent maturation of the DC membrane phenotype, until DCs reached a semi-mature state, with an upregulation of the membrane expression of CD86, CD83, HLA-DR and TLR4, associated with a down-regulation of DC-SIGN, MR and CD14. Measurement of the DC-secreted cytokines showed that Lcr35 induced a strong dose-dependent increase of the pro-Th1/Th17 cytokine levels (TNFα, IL-1β, IL-12p70, IL-12p40 and IL-23), but only a low increase in IL-10 concentration. The probiotic L. rhamnosus Lcr35 therefore induce a dose-dependent immunomodulation of human DCs leading, at high doses, to the semi-maturation of the cells and to a strong pro-inflammatory effect. These results contribute to a fuller understanding of the mechanism of action of this probiotic, and thus of its potential clinical indications in the treatment of either infectious or IgE-dependent allergic diseases.
authors.affiliation: CHU Clermont-Ferrand, Laboratoire d'Immunologie, Clermont-Ferrand, France. bevrard@chu-clermontferrand.fr
authors.forename: Bertrand
authors.initials: B
authors.lastname: Evrard
authors.forename: Sophie
authors.initials: S
authors.lastname: Coudeyras
authors.forename: Annie
authors.initials: A
authors.lastname: Dosgilbert
authors.forename: Nicolas
authors.initials: N
authors.lastname: Charbonnel
authors.forename: Josette
authors.initials: J
authors.lastname: Alamé
authors.forename: Arlette
authors.initials: A
authors.lastname: Tridon
authors.forename: Christiane
authors.initials: C
authors.lastname: Forestier
mesh_terms: D003713:Dendritic Cells / Q000382:microbiology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D052201:Lacticaseibacillus rhamnosus; D019936:Probiotics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic