Bifidobacterium infantis35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells

Abstract

BackgroundIntestinal homoeostasis is dependent on immunological tolerance to the microbiota. Objective To (1) determine if a probiotic could induce Foxp3 T cells in humans; (2) to elucidate the molecular mechanisms, which are involved in the induction of Foxp3 T cells by human dendritic cells. Design Cytokine secretion and Foxp3 expression were assessed in human volunteers following Bifidobacterium infantis feeding. Monocyte-derived dendritic cells (MDDCs), myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) were incubated in vitro with B infantis and autologous lymphocytes. Transcription factor expression, costimulatory molecule expression, cytokine secretion, retinoic acid and tryptophan metabolism were analysed. Results Volunteers fed B infantis displayed a selective increase in secretion of interleukin (IL)-10 and enhanced Foxp3 expression in peripheral blood. In vitro, MDDCs, mDCs and pDCs expressed indoleamine 2,3-dioxygenase and secreted IL-10, but not IL-12p70, in response to B infantis. MDDC and mDC IL-10 secretion was Toll-like receptor (TLR)-2/6 dependent, while pDC IL-10 secretion was TLR-9 dependent. In addition, MDDCs and mDCs expressed RALDH2, which was TLR-2 and DC-SIGN dependent. B infantis-stimulated MDDCs, mDCs and pDCs induced T cell Foxp3 expression. TLR-2, DC-SIGN and retinoic acid were required for MDDC and mDC induction of Foxp3 T cells, while pDCs required indoleamine 2,3-dioxygenase. Conclusions B infantis administration to humans selectively promotes immunoregulatory responses, suggesting that this microbe may have therapeutic utility in patients with inflammatory disease. Cross-talk between multiple pattern-recognition receptors and metabolic pathways determines the innate and subsequent T regulatory cell response to B infantis. These findings link nutrition, microbiota and the induction of tolerance within the gastrointestinal mucosa.

Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics

“…An increasingly recognised feature of immunoregulatory microbes is their ability to induce Treg cells [87]. It has been demonstrated that oral consumption of Bifidobacterium infantis 35624 is associated with enhanced IL-10 secretion and FoxP3 expression in human peripheral blood [89]. Murine studies have demonstrated that B. infantis administration results in an increase in CD4 + CD25 + FoxP3 + lymphocytes [90].…”

“…Murine studies have demonstrated that B. infantis administration results in an increase in CD4 + CD25 + FoxP3 + lymphocytes [90]. Moreover, it has been seen that, in vitro human dendritic cells stimulated with B. infantis selectively promoted the upregulation of FoxP3 expression in naïve lymphocytes [89]. Furthermore, B. infantis has been demonstrated to reduce symptom severity in patients with inflammatory bowel syndrome in two placebo-controlled human clinical studies [91,92].…”

Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization

“…15 Through the engagement of innate receptors, such as Toll-like receptors (TLRs), nucleotide-binding oligomerization domains (NODs) or C-type lectin receptors, probiotic lactobacilli and bifidobacteria induce distinct innate responses and cytokine profiles that subsequently shape T-helper cell responses. [16][17][18] There is accumulating evidence that certain strains possess intrinsic Th1-type immunomodulatory properties, 18,19 while others are able to induce regulatory responses. 17,20,21 Transforming growth factor (TGF)-b is present at high concentrations in the intestine and has a crucial involvement in modulating the immune response.…”

“…[16][17][18] There is accumulating evidence that certain strains possess intrinsic Th1-type immunomodulatory properties, 18,19 while others are able to induce regulatory responses. 17,20,21 Transforming growth factor (TGF)-b is present at high concentrations in the intestine and has a crucial involvement in modulating the immune response. 22 It has been shown to inhibit the proliferation and differentiation of both B and T cells, 23 and altered TGF-b signaling has been linked to the development of allergic disease.…”

Potentials of probiotics in the treatment of food allergy - a review

“…Konieczna et al (2011) determined that a probiotic could induce Foxp3 T cells in humans. Volunteers fed with B. infantis displayed selective increase in secretion of interleukins and enhanced Foxp3 expression in peripheral blood.…”