title: Saccharomyces boulardii inhibits lipopolysaccharide-induced activation of human dendritic cells and T cell proliferation.
abstract: Saccharomyces boulardii (Sb) is a probiotic yeast preparation that has demonstrated efficacy in inflammatory and infectious disorders of the gastrointestinal tract in controlled clinical trials. Although patients clearly benefit from treatment with Sb, little is known on how Sb unfolds its anti-inflammatory properties in humans. Dendritic cells (DC) balance tolerance and immunity and are involved critically in the control of T cell activation. Thus, they are believed to have a pivotal role in the initiation and perpetuation of chronic inflammatory disorders, not only in the gut. We therefore decided to investigate if Sb modulates DC function. Culture of primary (native, non-monocyte-derived) human myeloid CD1c+CD11c+CD123(-) DC (mDC) in the presence of Sb culture supernatant (active component molecular weight < 3 kDa, as evaluated by membrane partition chromatography) reduced significantly expression of the co-stimulatory molecules CD40 and CD80 (P < 0.01) and the DC mobilization marker CC-chemokine receptor CCR7 (CD197) (P < 0.001) induced by the prototypical microbial antigen lipopolysaccharide (LPS). Moreover, secretion of key proinflammatory cytokines such as tumour necrosis factor-alpha and interleukin (IL)-6 were notably reduced, while the secretion of anti-inflammatory IL-10 increased. Finally, Sb supernatant inhibited the proliferation of naive T cells in a mixed lymphocyte reaction with mDC. In summary, our data suggest that Sb may exhibit part of its anti-inflammatory potential through modulation of DC phenotype, function and migration by inhibition of their immune response to bacterial microbial surrogate antigens such as LPS.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, Charité Medical Center-Virchow Hospital, Medical School of the Humboldt-University of Berlin, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.forename: I
authors.initials: I
authors.lastname: Przesdzing
authors.forename: D
authors.initials: D
authors.lastname: Metzke
authors.forename: J
authors.initials: J
authors.lastname: Schmitz
authors.forename: A
authors.initials: A
authors.lastname: Radbruch
authors.forename: D C
authors.initials: DC
authors.lastname: Baumgart
mesh_terms: D018122:B7-1 Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000032:analysis; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008970:Molecular Weight; D019936:Probiotics; D054400:Receptors, CCR7 / Q000032:analysis; D012440:Saccharomyces / Q000276:immunology*
chemical_list: D018122:B7-1 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D008070:Lipopolysaccharides; D054400:Receptors, CCR7