title: Fungal β-glucan, a Dectin-1 ligand, promotes protection from type 1 diabetes by inducing regulatory innate immune response.
abstract: β-Glucans are naturally occurring polysaccharides in cereal grains, mushrooms, algae, or microbes, including bacteria, fungi, and yeast. Immune cells recognize these β-glucans through a cell surface pathogen recognition receptor called Dectin-1. Studies using β-glucans and other Dectin-1 binding components have demonstrated the potential of these agents in activating the immune cells for cancer treatment and controlling infections. In this study, we show that the β-glucan from Saccharomyces cerevisiae induces the expression of immune regulatory cytokines (IL-10, TGF-β1, and IL-2) and a tolerogenic enzyme (IDO) in bone marrow-derived dendritic cells as well as spleen cells. These properties can be exploited to modulate autoimmunity in the NOD mouse model of type 1 diabetes (T1D). Treatment of prediabetic NOD mice with low-dose β-glucan resulted in a profound delay in hyperglycemia, and this protection was associated with increase in the frequencies of Foxp3(+), LAP(+), and GARP(+) T cells. Upon Ag presentation, β-glucan-exposed dendritic cells induced a significant increase in Foxp3(+) and LAP(+) T cells in in vitro cultures. Furthermore, systemic coadministration of β-glucan plus pancreatic β cell Ag resulted in an enhanced protection of NOD mice from T1D as compared with treatment with β-glucan alone. These observations demonstrate that the innate immune response induced by low-dose β-glucan is regulatory in nature and can be exploited to modulate T cell response to β cell Ag for inducing an effective protection from T1D.
authors.affiliation: Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612;
authors.forename: Subha
authors.initials: S
authors.lastname: Karumuthil-Melethil
authors.affiliation: Department of Surgery, College of Medicine, Medical University of South Carolina, Charleston, SC 29425; and.
authors.forename: Radhika
authors.initials: R
authors.lastname: Gudi
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Medical University of South Carolina, Charleston, SC 29425.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Johnson
authors.affiliation: Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612;
authors.forename: Nicolas
authors.initials: N
authors.lastname: Perez
authors.affiliation: Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612; Department of Surgery, College of Medicine, Medical University of South Carolina, Charleston, SC 29425; and Department of Microbiology and Immunology, College of Medicine, Medical University of South Carolina, Charleston, SC 29425 vasu@musc.edu.
authors.forename: Chenthamarakshan
authors.initials: C
authors.lastname: Vasu
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004306:Dose-Response Relationship, Immunologic; D062610:Fungal Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects*; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000473:pathology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D012441:Saccharomyces cerevisiae / Q000737:chemistry*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D047071:beta-Glucans / Q000737:chemistry / Q000494:pharmacology*; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D062610:Fungal Polysaccharides; D037181:Lectins, C-Type; D047071:beta-Glucans; D000099181:Dectin-1