β-Glucans in food modify colonic microflora by inducing antimicrobial protein, calprotectin, in a Dectin-1-induced-IL-17F-dependent manner

Mucosal Immunol. 2018 May;11(3):763-773. doi: 10.1038/mi.2017.86. Epub 2017 Oct 25.

Abstract

Dectin-1 (gene symbol: Clec7a) is a receptor for β-glucans that play an important role for the host defense against fungi. Recently, we showed that Clec7a-/- mice are resistant against dextran sodium sulfate (DSS)-induced colitis because of regulatory T-cell population expansion in the colon. The regulatory T-cell expansion is caused by expansion of commensal Lactobacillus murinus whose growth is suppressed by an antimicrobial protein, calprotectin S100A8/A9. In this report, we showed that S100A8 was mainly produced by mouse colonic epithelial cells. S100A8 was not induced directly by Dectin-1 but by Dectin-1-induced cytokines, especially interleukin-17F (IL-17F), that were produced by several types of innate immune cells including CD11c+/CD11b+ myeloid cells in colonic lamina propria. S100A8/A9 heterodimer preferentially suppressed the growth of L. murinus that was increased in both Clec7a-/- and Il17f-/- mice. Furthermore, similar expansion of L. murinus and DSS-colitis resistance were observed in mice fed with β-glucan-free food. These observations suggest that food-derived β-glucans control the specific commensal microbiota via the Dectin-1-IL-17F-calprotectin axis to maintain the intestinal homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / metabolism
  • Calgranulin A / metabolism
  • Colitis / chemically induced
  • Colitis / genetics
  • Colitis / immunology*
  • Colon / immunology*
  • Food
  • Gastrointestinal Microbiome / physiology*
  • Host Microbial Interactions
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Intestinal Mucosa / physiology*
  • Lactobacillus / physiology*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Leukocyte L1 Antigen Complex / genetics
  • Leukocyte L1 Antigen Complex / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Cells / physiology*
  • beta-Glucans / administration & dosage*
  • beta-Glucans / metabolism

Substances

  • Anti-Infective Agents
  • Calgranulin A
  • Interleukin-17
  • Lectins, C-Type
  • Leukocyte L1 Antigen Complex
  • beta-Glucans
  • dectin 1