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