Intestinal Macrophages Balance Inflammatory Expression Profiles via Vitamin A and Dectin-1-Mediated Signaling

Front Immunol. 2020 Mar 31:11:551. doi: 10.3389/fimmu.2020.00551. eCollection 2020.

Abstract

Tissue resident intestinal macrophages are known to exhibit an anti-inflammatory phenotype and produce little pro-inflammatory cytokines upon TLR ligation, allowing symbiotic co-existence with the intestinal microbiota. However, upon acute events such as epithelial damage and concomitant influx of microbes, these macrophages must be able to quickly mount a pro-inflammatory response while more inflammatory macrophages are recruited from the blood stream simultaneously. Here, we show that dietary intake of vitamin A is required for the maintenance of the anti-inflammatory state of tissue resident intestinal macrophages. Interestingly, these anti-inflammatory macrophages were characterized by high levels of Dectin-1 expression. We show that Dectin-1 expression is enhanced by the vitamin A metabolite retinoic acid and our data suggests that Dectin-1 triggering might provide a switch to induce a rapid production of pro-inflammatory cytokines. In addition, Dectin-1 stimulation resulted in an altered metabolic profile which is linked to a pro-inflammatory response. Together, our data suggests that presence of vitamin A in the small intestine enhances an anti-inflammatory phenotype as well as Dectin-1 expression by macrophages and that this anti-inflammatory phenotype can rapidly convert toward a pro-inflammatory state upon Dectin-1 signaling.

Keywords: Dectin-1; anti-inflammatory; macrophage; pro-inflammatory; retinoic acid; small intestine; vitamin A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Inflammation / immunology*
  • Intestines / immunology*
  • Lectins, C-Type / immunology*
  • Lectins, C-Type / metabolism
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Mice, Inbred C57BL
  • Signal Transduction / immunology
  • Tretinoin / metabolism*
  • Tretinoin / pharmacology
  • Vitamin A / metabolism
  • Vitamin A / pharmacology

Substances

  • Lectins, C-Type
  • dectin 1
  • Vitamin A
  • Tretinoin