Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, People's Republic of China.
Laboratory of Developmental Biology and Regenerative Medicine, School of Medicine, South China University of Technology, Guangzhou 510006, People's Republic of China.
Open Biol. 2017 Aug;7(8). doi: 10.1098/rsob.170040.
Neutrophils play important roles in innate immunity and are mainly dependent on various enzyme-containing granules to kill engulfed microorganisms. Zebrafish () is specifically expressed in neutrophils; however, its function is largely unknown. Here, we generated an mutant ( ) via CRISPR/Cas9 to investigate the function of Npsn. The overall development and number of neutrophils remained unchanged in -deficient mutants, whereas neutrophil antibacterial function was defective. Upon infection with , the mutants exhibited a lower survival rate and more severe bacterial burden, as well as augmented inflammatory response to challenge with infection when compared with wild-type embryos, whereas -overexpressing zebrafish exhibited enhanced host defence against infection. These findings demonstrated that zebrafish Npsn promotes host defence against bacterial infection. Furthermore, our findings suggested that -deficient and -overexpressing zebrafish might serve as effective models of innate immunity.
中性粒细胞在先天免疫中发挥重要作用,主要依赖于各种含有酶的颗粒来杀死吞噬的微生物。斑马鱼 ()特异性表达于中性粒细胞;然而,其功能在很大程度上尚不清楚。在这里,我们通过 CRISPR/Cas9 生成了一个 ()突变体,以研究 Npsn 的功能。中性粒细胞缺陷突变体的整体发育和数量保持不变,而中性粒细胞的抗菌功能却有缺陷。在感染时,与野生型胚胎相比,突变体的存活率较低,细菌负荷量更高,对感染的炎症反应增强,而过表达斑马鱼则表现出对感染的宿主防御增强。这些发现表明,斑马鱼 Npsn 促进了宿主对细菌感染的防御。此外,我们的研究结果表明,中性粒细胞缺陷和过表达斑马鱼可能成为 先天免疫的有效模型。