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.

Dose-Dependent Effects of Lactobacillus rhamnosus on Serum Interleukin-17 Production and Intestinal T-Cell Responses in Pigs Challenged with Escherichia coli

“…Previously, we have shown that pretreatment of piglets with L. rhamnosus increases in the number of lactobacilli and bifidobacteria accompanied by a reduction in coliform shedding in feces by day 9 (i.e., 24 h after F4 ϩ ETEC challenge) (22). Similarly, the probiotic L. rhamnosus strain Lcr35 was shown to induce a strong dose-dependent increase in the production of pro-Th1/Th17 cytokines by human dendritic cells (32). The serum concentration of IL-10 changed in a similar manner to that of IL-17A in our experiments, although the changes were not statistically significant.…”

Further studies on immunomodulatory effects of exopolysaccharide isolated from Lactobacillus rhamnosus KL37C

“…LTA also stimulated macro- site effect in the case of use of Bifidobacterium bacteria [28]. Evrard et al showed that L. rhamnosus Lcr35 increased synthesis of the Th1/Th17 cytokine profile, but had no significant effect on the level of IL-10 [29]. Previously, we have demonstrated the impact of EPS 37 on humoral immune response in mice.…”

Expression of cytokines in chicken peripheral mononuclear blood cells (PMBCs) exposed to probiotic strains and Salmonella Enteritidis

“…Some strains modulate the cytokine production in vitro and induce a regulatory response, whereas others induce a pro-inflammatory response (Evrard et al 2011). However, several studies have provided unequivocal evidence that the specific strains of probiotics are able to stimulate multiple aspects of innate immunity (Weiss et al 2010) as well as to increase the humoral immunity (Roberfroid 2002).…”