Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu 610041, PR China; Key Laboratory of Animal Science of State Ethnic Affairs Commission, Southwest Minzu University, Chengdu 610041, PR China.
Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu 610041, PR China; Key Laboratory of Animal Science of State Ethnic Affairs Commission, Southwest Minzu University, Chengdu 610041, PR China.
Bioorg Chem. 2024 May;146:107245. doi: 10.1016/j.bioorg.2024.107245. Epub 2024 Mar 4.
The overuse of antibiotics has led to the enhanced resistance of many pathogenic bacteria, posing a threat to human health. Therefore, there is a need to develop green and safe alternatives to antibiotics. Beta-defensins play a crucial role in host defense against pathogens and have multifunctional properties, exerting key roles in innate and adaptive immunity, as well as non-immune processes. In this study, a 210 bp long cDNA sequence of yak DEFB114 gene was amplified and successfully expressed in a prokaryotic system. The DEFB114 protein exhibited significant inhibitory effects on the growth of Aspergillus fumigatus in vitro. When co-cultured with yak macrophages, DEFB114 protein enhanced macrophage phagocytic activity and increased nucleic acid fluorescence intensity (P < 0.05). DEFB114 protein also enhanced the activity of yak macrophages stimulated by inactivated Aspergillus fumigatus spores, increased the release of nitric oxide (NO), and promoted the expression of genes such as γ-actin, Lgals, Man2b, and Capg (P < 0.05). In mice experiments, DEFB114 protein promoted resistance against Aspergillus fumigatus infection, by regulating the NOD1/2-ATG16L1-NF-κB pathway to modulate the host immune response and exert its anti-infective effects. In summary, the yak DEFB114 protein could inhibit the growth of Aspergillus fumigatus and enhance the animal's resistance to pathogenic microorganisms, thereby having significant implications in the treatment and prevention of fungal infections.
抗生素的过度使用导致许多病原菌的耐药性增强，对人类健康构成威胁。因此，需要开发绿色、安全的抗生素替代品。β-防御素在宿主防御病原体方面发挥着重要作用，具有多功能特性，在先天免疫和适应性免疫以及非免疫过程中发挥关键作用。在本研究中，扩增并成功在原核系统中表达了牦牛 DEFB114 基因的 210bp 长 cDNA 序列。DEFB114 蛋白对烟曲霉的体外生长具有显著的抑制作用。当与牦牛巨噬细胞共培养时，DEFB114 蛋白增强了巨噬细胞的吞噬活性并增加了核酸荧光强度（P<0.05）。DEFB114 蛋白还增强了被灭活烟曲霉孢子刺激的牦牛巨噬细胞的活性，增加了一氧化氮（NO）的释放，并促进了γ-肌动蛋白、Lgals、Man2b 和 Capg 等基因的表达（P<0.05）。在小鼠实验中，DEFB114 蛋白通过调节 NOD1/2-ATG16L1-NF-κB 通路来调节宿主免疫反应并发挥其抗感染作用，从而促进对烟曲霉感染的抵抗力。总之，牦牛 DEFB114 蛋白可以抑制烟曲霉的生长并增强动物对病原微生物的抵抗力，因此在真菌感染的治疗和预防方面具有重要意义。
