Cell surface polysaccharides of Bifidobacterium bifidum induce the generation of Foxp3 ⁺ regulatory T cells

Abstract

Dysregulation of intestinal microflora is linked to inflammatory disorders associated with compromised immunosuppressive functions of Foxp3+ T regulatory (Treg) cells. Although mucosa-associated commensal microbiota has been implicated in Treg generation, molecular identities of the “effector” components controlling this process remain largely unknown. Here, we have defined Bifidobacterium bifidum as a potent inducer of Foxp3+ Treg cells with diverse T cell receptor specificity to dietary antigens, commensal bacteria, and B. bifidum itself. Cell surface β-glucan/galactan (CSGG) polysaccharides of B. bifidum were identified as key components responsible for Treg induction. CSGG efficiently recapitulated the activity of whole bacteria and acted via regulatory dendritic cells through a partially Toll-like receptor 2–mediated mechanism. Treg cells induced by B. bifidum or purified CSGG display stable and robust suppressive capacity toward experimental colitis. By identifying CSGG as a functional component of Treg-inducing bacteria, our studies highlight the immunomodulatory potential of CSGG and CSGG-producing microbes.

Lysates ofMethylococcus capsulatusBath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+Tregs and improve metabolism

“…The substantial, consistent, and global changes in the immunometabolic profile found in this study point towards clinical potential if further developed. Notably, only a single study has previously succeeded in inducing p T regs , and this was limited to LI-LP 11 . Apart from inducing this cell subset throughout the gastrointestinal tract, we further show that these cells exhibited enhanced secretory capacity of IL-17 in WD McB -fed mice compared to their WD CNTL fed counterparts.…”

“…An alternative to administering viable microbes is to utilize whole cell lysates, or selected cell components, of non-living bacteria. Apart from alleviating global energy demands, if used as a nutrient source, such components may also potently affect host physiology as recently reported for A. muciniphila 10 and Bifidobacterium bifidum 11 . In the latter example, cell surface polysaccharides of B. bifidum were used to induce peripheral immune-tolerance via generation of regulatory T cells (T regs ).…”

“…In the latter example, cell surface polysaccharides of B. bifidum were used to induce peripheral immune-tolerance via generation of regulatory T cells (T regs ). The authors reported a pronounced increase in Foxp3 + RORγt + T regs ( p T regs ), specifically in lamina propria (LP) of the large intestine (LI) 11 . This cell type is believed to be induced by commensal microbes and has emerged as a potent T reg subset, exhibiting increased lineage stability and enhanced immunosuppressive capacity during intestinal inflammation compared to conventional Foxp3 + RORγt - T regs ( n T regs ) 12 .…”

Understanding immune–microbiota interactions in the intestine

“…A variety of bacterial strains from distinct phyla, operating individually or as part of multi-strain consortia, prime the accumulation of peripherally derived colonic Treg cells and the production of the immune suppressive cytokine IL-10. These include Clostridia from clusters IV, XIVa and XVIII (Firmicutes), 48,54 various Bacteroides species (Bacteroidetes) 68,78,83,96 or Helicobacter species (Proteobacteria), [97][98][99] Bifidobacterium bifidum (Actinobacteria), 100 and the Altered Schaedler Flora (multiple phyla). 101 An isolate of Bifidobacterium adolescentis (an Actinobacteria) obtained from humans that could induce Th17 cells was also identified, confirming that this was not unique to SFB.…”

Defining Dysbiosis in Inflammatory Bowel Disease

“…Moreover, monocolonization with individual bacterial strains or products from probiotic strains can also induce RORgt + Treg cells to a similar degree as in mice colonized with a specific-pathogen-free microbiota. Whether supplementation with one of those strains or products is able to induce tolerance toward a complex microbiota in a physiologic setting remains to be addressed (Sefik et al, 2015;Verma et al, 2018).…”