The Adaptor Protein CARD9 Protects against Colon Cancer by Restricting Mycobiota-Mediated Expansion of Myeloid-Derived Suppressor Cells

被引：169

作者：

Wang, Tingting ^{[1
,2
]}

Fan, Chaogang ^{[3
]}

Yao, Anran ^{[1
]}

Xu, Xingwei ^{[3
]}

Zheng, Guoxing ^{[4
,5
]}

You, Yun ^{[2
]}

Jiang, Changying ^{[2
]}

Zhao, Xueqiang ^{[4
]}

Hou, Yayi ^{[1
]}

Hung, Mien-Chie ^{[2
]}

Lin, Xin ^{[4
,5
]}

机构：

[1] Nanjing Univ, Sch Med, Jiangsu Key Lab Mol Med, State Key Lab Pharmaceut Biotechnol,Div Immunol, Nanjing 210093, Jiangsu, Peoples R China

[2] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[3] Nanjing Univ, Sch Med, Jinling Hosp, Gen Surg, Nanjing 210093, Jiangsu, Peoples R China

[4] Tsinghua Univ, Inst Immunol, Sch Med, Beijing 100084, Peoples R China

[5] Tsinghua Univ Peking Univ Joint Ctr Life Sci, Beijing 100084, Peoples R China

来源：

IMMUNITY | 2018年 / 49卷 / 03期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; GUT MICROBIOTA; COLORECTAL-CANCER; CANDIDA-ALBICANS; IMMUNE-RESPONSES; INTESTINAL INFLAMMATION; ANTIFUNGAL IMMUNITY; INNATE IMMUNE; HOST-DEFENSE;

D O I：

10.1016/j.immuni.2018.08.018

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The adaptor protein CARD9 links detection of fungi by surface receptors to the activation of the NF-kappa B pathway. Mice deficient in CARD9 exhibit dysbiosis and are more susceptible to colitis. Here we examined the impact of Card9 deficiency in the development of colitis-associated colon cancer (CAC). Treatment of Card9(-/-) ice with AOM-DSS resulted in increased tumor loads as compared to WT mice and in the accumulation of myeloid-derived suppressor cells (MDSCs) in tumor tissue. The impaired fungicidal functions of Card9(-/-) macrophages led to increased fungal loads and variation in the overall composition of the intestinal mycobiota, with a notable increase in C. tropicalis. Bone marrow cells incubated with C. tropicalis exhibited MDSC features and suppressive functions. Fluconazole treatment suppressed CAC in Card9(-/-) mice and was associated with decreased MDSC accumulation. The frequency of MDSCs in tumor tissues of colon cancer patients correlated positively with fungal burden, pointing to the relevance of this regulatory axis in human disease.

引用

页码：504 / +

页数：15

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