Telesford KM, Yan W, Ochoa-Reparaz J, Pant A, Kircher C, Christy MA, Begum-Haque S, Kasper DL, Kasper LH. A commensal symbiotic factor derived from Bacteroides fragilis promotes human CD39+Foxp3+ T cells and Treg function. Gut Microbes. 2015;6(4):234-242
There is a belief that the gut microbes can influence the immune system, which will impact on the course of MS. Bacteroides fragilis is an obligately anaerobic, Gram-negative, rod-shaped bacterium. It is part of the normal flora of the human colonand is generally commensal, but can cause infection if displaced into the bloodstream or surrounding tissue following surgery, disease, or trauma.Here polysaccharide A (PSA) derived from Bacteroides fragilis is a factor that stimulates immunologic development within mammalian hosts. PSA rebalances skewed systemic T helper responses and promotes T regulatory cells (Tregs). So could gut flora change MS susceptibility?
Polysaccharide A (PSA) derived from the human commensal Bacteroides fragilis is a symbiosis factor that stimulates immunologic development within mammalian hosts. PSA rebalances skewed systemic T helper responses and promotes T regulatory cells (Tregs). However, PSA-mediated induction of Foxp3 in humans has not been reported. In mice, PSA-generated Foxp3+ Tregs dampen Th17 activity thereby facilitating bacterial intestinal colonization while the increased presence and function of these regulatory cells may guard against pathological organ-specific inflammation in hosts. We herein demonstrate that PSA induces expression of Foxp3 along with CD39 among naïve CD4 T cells in vitro while promoting IL-10 secretion. PSA-activated dendritic cells are essential for the mediation of this regulatory response. When cultured with isolated Foxp3+ Tregs, PSA enriched Foxp3 expression, enhanced the frequency of CD39+HLA-DR+ cells, and increased suppressive function as measured by decreased TNFα expression by LPS-stimulated monocytes. Our findings are the first to demonstrate in vitro induction of human CD4+Foxp3+ T cells and enhanced suppressive function of circulating Foxp3+ Tregs by a human commensal bacterial symbiotic factor. Use of PSA for the treatment of human autoimmune diseases, in particular multiple sclerosis and inflammatory bowel disease, may represent a new paradigm in the approach to treating autoimmune disease.