Dectin-3 Deficiency Promotes Colitis Development due to Impaired Antifungal Innate Immune Responses in the Gut

PLoS Pathog. 2016 Jun 9;12(6):e1005662. doi: 10.1371/journal.ppat.1005662. eCollection 2016 Jun.


Interactions between commensal fungi and gut immune system are critical for establishing colonic homeostasis. Here we found that mice deficient in Dectin-3 (Clec4d-/-), a C-type lectin receptor that senses fungal infection, were more susceptible to dextran sodium sulfate (DSS)-induced colitis compared with wild-type mice. The specific fungal burden of Candida (C.) tropicalis was markedly increased in the gut after DSS treatment in Clec4d-/- mice, and supplementation with C. tropicalis aggravated colitis only in Clec4d-/- mice, but not in wild-type controls. Mechanistically, Dectin-3 deficiency impairs phagocytic and fungicidal abilities of macrophages, and C. tropicalis-induced NF-κB activation and cytokine production. The conditioned media derived from Dectin-3-deficient macrophages were defective in promoting tissue repairing in colonic epithelial cells. Finally, anti-fungal therapy was effective in treating colitis in Clec4d-/- mice. These studies identified the role of Dectin-3 and its functional interaction with commensal fungi in intestinal immune system and regulation of colonic homeostasis.

MeSH terms

  • Animals
  • Blotting, Western
  • Candida tropicalis*
  • Colitis / chemically induced
  • Colitis / immunology*
  • Colitis / microbiology
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Electrophoretic Mobility Shift Assay
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gastrointestinal Microbiome / immunology*
  • Immunity, Innate / immunology*
  • Immunoprecipitation
  • Lectins, C-Type / deficiency
  • Lectins, C-Type / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Real-Time Polymerase Chain Reaction
  • Receptors, Immunologic / deficiency
  • Receptors, Immunologic / immunology*


  • Clec4d protein, mouse
  • Lectins, C-Type
  • Receptors, Immunologic
  • Dextran Sulfate