Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
J Innate Immun. 2022;14(3):229-242. doi: 10.1159/000519183. Epub 2021 Sep 24.
Vitamin D (VD) is a major regulator of calcium metabolism in many living organisms. In addition, VD plays a key role in regulating innate and adaptive immunity in vertebrates. Neutrophils constitute an important part of the first line of defense against invading microbes; however, the potential effect of VD on neutrophils remains elusive. Thus, in this study zebrafish in different developmental stages were utilized to identify the potential role of VD in the basal homeostasis and functions of neutrophils. Our results showed that addition of exogenous VD3 promoted granulopoiesis in zebrafish larvae. Reciprocally, neutrophil abundance in the intestine of adult zebrafish with a cyp2r1 mutant, lacking the capacity to 25-hydroxylate VD, was reduced. Moreover, VD-mediated granulopoiesis was still observed in gnotobiotic zebrafish larvae, indicating that VD regulates neutrophil generation independent of the microbiota during early development. In contrast, VD was incapable to influence granulopoiesis in adult zebrafish when the commensal bacteria were depleted by antibiotic treatment, suggesting that VD might modulate neutrophil activity via different mechanisms depending on the developmental stage. In addition, we found that VD3 augmented the expression of il-8 and neutrophil recruitment to the site of caudal fin amputation. Finally, VD3 treatment significantly decreased bacterial counts and mortality in zebrafish infected with Edwardsiella tarda (E. tarda) in a neutrophil-dependent manner. Combined, these findings demonstrate that VD regulates granulopoiesis and neutrophil function in zebrafish immunity.
维生素 D（VD）是许多生物中钙代谢的主要调节剂。此外，VD 在脊椎动物先天和适应性免疫中起关键作用。中性粒细胞构成了抵御入侵微生物的第一道防线的重要组成部分；然而，VD 对中性粒细胞的潜在影响仍不清楚。因此，在这项研究中，利用不同发育阶段的斑马鱼来确定 VD 在中性粒细胞的基础稳态和功能中的潜在作用。我们的结果表明，外源性 VD3 促进了斑马鱼幼虫的粒细胞生成。相反，缺乏 25-羟化 VD 能力的 Cyp2R1 突变体成年斑马鱼肠道中的中性粒细胞丰度降低。此外，在无菌斑马鱼幼虫中仍观察到 VD 介导的粒细胞生成，表明 VD 在早期发育过程中独立于微生物群调节中性粒细胞的生成。相比之下，当用抗生素处理耗尽共生细菌时，VD 无法影响成年斑马鱼的粒细胞生成，这表明 VD 可能通过不同的机制来调节中性粒细胞的活性，具体取决于发育阶段。此外，我们发现 VD3 增强了 il-8 的表达，并促进了中性粒细胞向尾鳍切除部位的募集。最后，VD3 治疗以中性粒细胞依赖性方式显著降低了感染迟钝爱德华氏菌（E. tarda）的斑马鱼的细菌计数和死亡率。综上所述，这些发现表明 VD 调节斑马鱼免疫中的粒细胞生成和中性粒细胞功能。
