Dectin-3 Deficiency Promotes Colitis Development due to Impaired Antifungal Innate Immune Responses in the Gut.
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.
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.
Tingting
T
Wang
Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.|Cancer Biology Program, The University of Texas, Graduate School of Biomedical Sciences, Houston, Texas, United States of America.
Deng
D
Pan
Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.|Cancer Biology Program, The University of Texas, Graduate School of Biomedical Sciences, Houston, Texas, United States of America.
Zhicheng
Z
Zhou
Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
Yun
Y
You
Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
Changying
C
Jiang
Institute for Immunology, Tsinghua University School of Medicine, Beijing, China.
Xueqiang
X
Zhao
Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.|Cancer Biology Program, The University of Texas, Graduate School of Biomedical Sciences, Houston, Texas, United States of America.|Institute for Immunology, Tsinghua University School of Medicine, Beijing, China.
Xin
X
Lin
D000818:Animals; D015153:Blotting, Western; D041022:Candida tropicalis; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D047468:Immunoprecipitation; D037181:Lectins, C-Type / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000172:deficiency / Q000276:immunology*
C584161:Clec4d protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D016264:Dextran Sulfate