Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China.
Research Center for Medical Mycology, Peking University, Beijing, China.
Infect Immun. 2021 Apr 16;89(5). doi: 10.1128/IAI.00040-21.
is a frequently found fungus in Asia, especially China, and it causes primary cutaneous mucormycosis with a high rate of disfigurement. Caspase recruitment domain-containing protein 9 (Card9) is an essential adaptor molecule downstream of C-type lectin receptors. It mediates the activation of nuclear factor kappa B (NF-κB), regulates T helper 1 (Th1) and Th17 differentiation, and plays an important role in fungal immune surveillance. CARD9 deficiency correlates with the increased susceptibility to many fungal infections, including cutaneous mucormycosis caused by However, the underlying immunological mechanisms were not elucidated. Our study established a murine model of subcutaneous infection, and we isolated immune cells, including bone marrow-derived macrophages, bone marrow-derived dendritic cells, naive T cells, and neutrophils, from wild-type (WT) and knockout ( ) mice to examine the antifungal effect of Card9 on and mice exhibited increased susceptibility to infection. Impaired local cytokine and chemokine production, NF-κB (p65) activation, and Th1/17 cell differentiation and partially impaired neutrophil-dependent antifungal immunity were observed in mice. This work enriches our knowledge of the relationship between CARD9 deficiency and mucormycosis.
是一种在亚洲（尤其是中国）常见的真菌，可导致原发性皮肤毛霉菌病，且毁容率较高。衔接蛋白包含半胱氨酸天冬氨酸酶募集域蛋白 9（Card9）是 C 型凝集素受体下游的一种必需衔接分子。它介导核因子 kappa B（NF-κB）的激活，调节辅助性 T 细胞 1（Th1）和 Th17 分化，并在真菌免疫监视中发挥重要作用。Card9 缺失与多种真菌感染的易感性增加相关，包括由引起的皮肤毛霉菌病。然而，其潜在的免疫学机制尚不清楚。本研究建立了皮下感染的小鼠模型，并从野生型（WT）和 基因敲除（）小鼠中分离了免疫细胞，包括骨髓来源的巨噬细胞、骨髓来源的树突状细胞、幼稚 T 细胞和中性粒细胞，以研究 Card9 对 和 小鼠对 感染的易感性增加。在 小鼠中观察到局部细胞因子和趋化因子产生、NF-κB（p65）激活、Th1/17 细胞分化受损以及中性粒细胞依赖性抗真菌免疫部分受损。这项工作丰富了我们对 Card9 缺失与毛霉菌病之间关系的认识。
