Abstract
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.
Original language | English (US) |
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Article number | e1005662 |
Journal | PLoS pathogens |
Volume | 12 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2016 |
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Immunology
- Molecular Biology
- Genetics
- Virology
MD Anderson CCSG core facilities
- Genetically Engineered Mouse Facility
- Research Animal Support Facility