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

PLoS Pathogens

Xueqiang Zhao¹  Yun You¹  Tingting Wang²  Xin Lin²  Changying Jiang²  Zhicheng Zhou²  Deng Pan³ 

[1] Cancer Biology Program, The University of Texas, Graduate School of Biomedical Sciences, Houston, Texas, United States of America;Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America;The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China

关键词: Colon;    Colitis;    Gastrointestinal tract;    Fungi;    Transcription factors;    Cytokines;    Macrophages;    Inflammation;   

DOI  :  10.1371/journal.ppat.1005662

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY