Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, College of Fisheries, Huazhong Agricultural University, Wuhan, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
Front Immunol. 2019 Nov 8;10:2599. doi: 10.3389/fimmu.2019.02599. eCollection 2019.
Copper has been revealed to negatively affect the hematopoietic system, which has an important function in immune pathogen defense, but little is known about the potential mechanism. In this study, copper-stressed larvae exhibited significantly increased mortality as well as reduced percentages of GFP-labeled macrophages and neutrophils after () infection. However, those copper-stressed GFP-labeled macrophages and neutrophils showed more rapid responses to infection. The transcriptional profiles in copper-stressed macrophages or neutrophils were unveiled by RNA-Sequencing, and KEGG pathway analysis revealed enrichment of differentially expressed genes (DEGs) in lysosome, apoptosis, oxidative phosphorylation, phagosome, etc. The copper-stressed macrophages or neutrophils were revealed to have an increase in reactive oxygen species (ROS) and mitochondria ROS (mROS)-mediated apoptosis, and a reduction in phagocytosis. Furthermore, the infected copper-stressed macrophages or neutrophils were found to be unable to maintain a consistently increased expression in immune responsive genes. This study demonstrated for the first time that copper might induce the susceptibility of fish larvae to inflammatory stimuli triggering macrophage or neutrophil apoptosis, leading to reduced phagocytic activities and non-sustainable immune responses in immune macrophages or neutrophils.
铜已被证明会对造血系统产生负面影响，造血系统在免疫病原体防御中起着重要作用，但对其潜在机制知之甚少。在这项研究中，铜胁迫的幼虫在 （）感染后表现出明显更高的死亡率，以及 GFP 标记的巨噬细胞和中性粒细胞百分比降低。然而，那些铜胁迫的 GFP 标记的巨噬细胞和中性粒细胞对 感染的反应更快。通过 RNA 测序揭示了铜胁迫的巨噬细胞或中性粒细胞的转录谱，KEGG 途径分析显示溶酶体、细胞凋亡、氧化磷酸化、吞噬体等差异表达基因（DEGs）富集。铜胁迫的巨噬细胞或中性粒细胞表现出活性氧（ROS）和线粒体 ROS（mROS）介导的细胞凋亡增加，吞噬作用减少。此外，还发现感染的铜胁迫的巨噬细胞或中性粒细胞不能维持免疫反应基因的持续高表达。本研究首次表明，铜可能会诱导鱼类幼虫对炎症刺激的敏感性，从而触发巨噬细胞或中性粒细胞凋亡，导致免疫巨噬细胞或中性粒细胞的吞噬活性降低和非持续的免疫反应。
