Fungal β-glucan, a Dectin-1 ligand, promotes protection from type 1 diabetes by inducing regulatory innate immune response

J Immunol. 2014 Oct 1;193(7):3308-21. doi: 10.4049/jimmunol.1400186. Epub 2014 Aug 20.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Dose-Response Relationship, Immunologic
  • Fungal Polysaccharides / chemistry
  • Fungal Polysaccharides / pharmacology*
  • Immunity, Innate / drug effects*
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / pathology
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Saccharomyces cerevisiae / chemistry*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • beta-Glucans / chemistry
  • beta-Glucans / pharmacology*

Substances

  • Cytokines
  • Fungal Polysaccharides
  • Lectins, C-Type
  • beta-Glucans
  • dectin 1