A Novel Probiotic Mixture Exerts a Therapeutic Effect on Experimental Autoimmune Encephalomyelitis Mediated by IL-10 Producing Regulatory T Cells

Abstract

BackgroundMultiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). One potential therapeutic strategy for MS is to induce regulatory cells that mediate immunological tolerance. Probiotics, including lactobacilli, are known to induce immunomodulatory activity with promising effects in inflammatory diseases. We tested the potential of various strains of lactobacilli for suppression of experimental autoimmune encephalomyelitis (EAE), an animal model of MS.Methodology/Principal FindingsThe preventive effects of five daily-administered strains of lactobacilli were investigated in mice developing EAE. After a primary screening, three Lactobacillus strains, L. paracasei DSM 13434, L. plantarum DSM 15312 and DSM 15313 that reduced inflammation in CNS and autoreactive T cell responses were chosen. L. paracasei and L. plantarum DSM 15312 induced CD4+CD25+Foxp3+ regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) and enhanced production of serum TGF-β1, while L. plantarum DSM 15313 increased serum IL-27 levels. Further screening of the chosen strains showed that each monostrain probiotic failed to be therapeutic in diseased mice, while a mixture of the three lactobacilli strains suppressed the progression and reversed the clinical and histological signs of EAE. The suppressive activity correlated with attenuation of pro-inflammatory Th1 and Th17 cytokines followed by IL-10 induction in MLNs, spleen and blood. Additional adoptive transfer studies demonstrated that IL-10 producing CD4+CD25+ Tregs are involved in the suppressive effect induced by the lactobacilli mixture.Conclusions/SignificanceOur data provide evidence showing that the therapeutic effect of the chosen mixture of probiotic lactobacilli was associated with induction of transferable tolerogenic Tregs in MLNs, but also in the periphery and the CNS, mediated through an IL-10-dependent mechanism. Our findings indicate a therapeutic potential of oral administration of a combination of probiotics and provide a more complete understanding of the host-commensal interactions that contribute to beneficial effects in autoimmune diseases.

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“…Segmented filamentous bacteria have been positively correlated with EAE (29). In contrast, B. fragilis, Bifidobacterium sp., and some strains of Lactobacillus negatively correlate with EAE (69)(70)(71)(72). Evidence is now also emerging for a role by commensal microbiota in the etiology of human MS. Faecalibacterium (phylum Firmicutes) has been found in low abundance in untreated MS patients, and this was reversed by glatimer acetate (GA) treatment (73).…”

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

“…In this regard, it is interesting that the immunoregulatory effects of probiotic microorganisms are also thought to occur through the generation of T regs and the synthesis and secretion of IL-10 (Lavasani et al, 2010). Feeding of a commensal bacteria to GF mice results in local DC uptake and alteration of phenotype to one which promotes T reg production and IL-10 synthesis.…”

Functional plasticity in human FOXP3+regulatory T cells

“…Both have proven to be efficacious in mouse models of autoimmunity. [17][18][19][20][21] These encouraging results have made vaccines and cellular transfer therapy important avenues currently pursued in clinical trials. 22 Approaches selectively favoring the survival of Treg cells include the provision of low doses of IL-2, or the use of immunosuppressive pharmaceutical agents such as Cyclosporin A and Rapamycin, which have recently been found to selectively modulate biochemical pathways in Tconv or Treg cells.…”