PLoS Pathogens | |
Dectin-3 Deficiency Promotes Colitis Development due to Impaired Antifungal Innate Immune Responses in the Gut | |
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
【 预 览 】
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