Developmental and comparative immunology最新文献_第3页

Peroxiredoxin 4 from amphioxus: An antioxidant enzyme with immunomodulatory roles in defense against Vibrio anguillarum 文昌鱼过氧化氧还蛋白4：一种具有免疫调节作用的抗氧化酶，用于防御鳗弧菌。

IF 2.4 3区农林科学 Q1 FISHERIES

Developmental and comparative immunology

Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.dci.2026.105550

Bangyao Liang , Wei Meng , Meihan Chen , Hongfei Miao , Yuhan Ren , Hongyu Liu , Zhenhui Liu , Chen Sun

Peroxiredoxin 4 (Prdx4), a typical 2-Cys peroxiredoxin, functions as both an antioxidant enzyme and a regulator of immune processes, yet its roles in early chordates remain unclear. Here, we identified and characterized a Prdx4 homolog from amphioxus (Branchiostoma japonicum), termed BjPrdx4. Sequence analyses revealed conserved catalytic motifs and an N-terminal signal peptide, supporting its classification as Prdx4. BjPrdx4 was constitutively expressed across multiple tissues, with prominent localization in immune-associated tissues, and its expression was markedly induced following Vibrio anguillarum challenge. Infection also triggered BjPrdx4 secretion into the extracellular milieu and altered its oligomeric states. Recombinant BjPrdx4 exhibited robust thiol-dependent peroxidase activity, efficiently eliminating hydrogen peroxide and protecting plasmid DNA from oxidative damage, confirming its antioxidant function. Functionally, extracellular BjPrdx4 preserved gill integrity and reduced bacterial burden during infection. Transcriptomic and qRT-PCR analyses further demonstrated that BjPrdx4 influenced immune-related pathways, including phagocytosis and lysosomal activity, and positively regulated ras expression, suggesting involvement in Ras–MAPK signaling. Together, these findings reveal that BjPrdx4 integrates antioxidant defense with immunomodulatory functions, highlighting its dual role in amphioxus antibacterial immunity and underscoring the evolutionary significance of Prdx4 multifunctionality in basal chordates.

过氧还蛋白4 （Prdx4）是一种典型的2-胱氨酸过氧还蛋白，它既是一种抗氧化酶，也是一种免疫过程的调节剂，但其在早期脊索动物中的作用尚不清楚。在这里，我们从文昌鱼（Branchiostoma japonicum）中鉴定并鉴定了一个Prdx4同源物，命名为BjPrdx4。序列分析显示保守的催化基序和一个n端信号肽，支持其归类为Prdx4。BjPrdx4在多个组织中组成性表达，在免疫相关组织中有明显的定位，在鳗弧菌攻毒后其表达被显著诱导。感染也触发BjPrdx4分泌到细胞外环境，并改变其寡聚物状态。重组BjPrdx4表现出较强的巯基依赖性过氧化物酶活性，能有效去除过氧化氢，保护质粒DNA免受氧化损伤，证实了其抗氧化功能。在功能上，胞外BjPrdx4保存了鳃的完整性，减少了感染期间的细菌负担。转录组学和qRT-PCR分析进一步表明，BjPrdx4影响免疫相关途径，包括吞噬和溶酶体活性，并积极调节ras表达，提示参与ras - mapk信号通路。综上所述，这些发现表明BjPrdx4整合了抗氧化防御和免疫调节功能，突出了其在文文鱼抗菌免疫中的双重作用，并强调了Prdx4多功能性在基础脊索动物中的进化意义。

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引用次数: 0

Cloning and their roles in NF-κB, IFN-β, and AP-1 signaling pathways of AKT1 and AKT2 genes of largemouth bass (Micropterus salmoides) 大口黑鲈AKT1和AKT2基因的克隆及其在NF-κB、IFN-β和AP-1信号通路中的作用

IF 2.4 3区农林科学 Q1 FISHERIES

Developmental and comparative immunology

Pub Date : 2026-02-01 Epub Date: 2026-01-09 DOI: 10.1016/j.dci.2026.105547

Junjian Dong , Jiaxin Li , Zhi lin Zhu , Hetong Zhang , Chengfei Sun , Fengying Gao , Xing Ye

To elucidate the regulatory role of the AKT gene (Protein Kinase B) in the NF-κB, IFN and AP-1 signalling pathways in largemouth bass, the open reading frame (ORF) sequences of the AKT1 and AKT2 genes were isolated from largemouth bass (Micropterus salmoides). AKT1 and AKT2 possessed a conserved Pleckstrin homology (PH) domain, a catalytic serine/threonine kinase domain (STKc), and a specific serine/threonine kinase family domain (STKX). AKT1 was most highly expressed in the spleen, whereas AKT2 showed the highest expression in the blood. Infection with N. seriolae, Poly (I:C), and LMBV significantly induced the expression of AKT1 and AKT2 in largemouth bass. Overexpression of AKT1 and AKT2 did not significantly increased the NF-κB promoter activity; however, significantly activated the AP-1 and IFN-β promoters. Subcellular localisation analysis showed that AKT1 was distributed in both the cytoplasm and nucleus, whereas AKT2 was predominantly localised in the cytoplasm, with weak nuclear signals. Pull-down analysis revealed no interaction between AKT-IP or AKT-IP-like proteins and AKT1, whereas a direct interaction was observed with AKT2. These findings provide insight into the immune regulatory roles of AKT in teleosts.

为了阐明AKT基因（蛋白激酶B）在大口黑鲈NF-κB、IFN和AP-1信号通路中的调控作用，我们从大口黑鲈（Micropterus salmoides）中分离到了AKT1和AKT2基因的开放阅读框（ORF）序列。AKT1和AKT2具有一个保守的Pleckstrin同源结构域（PH）、一个催化丝氨酸/苏氨酸激酶结构域（STKc）和一个特定的丝氨酸/苏氨酸激酶家族结构域（STKX）。AKT1在脾脏中表达最高，而AKT2在血液中表达最高。大肠杆菌、Poly （I:C）和LMBV感染可显著诱导大口黑鲈AKT1和AKT2的表达。过表达AKT1和AKT2未显著提高NF-κB启动子活性；然而，显著激活AP-1和IFN-β启动子。亚细胞定位分析表明，AKT1分布在细胞质和细胞核中，而AKT2主要分布在细胞质中，核信号较弱。下拉分析显示，AKT-IP或AKT-IP样蛋白与AKT1之间没有相互作用，而与AKT2直接相互作用。这些发现为了解AKT在硬骨鱼中的免疫调节作用提供了新的思路。

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引用次数: 0

miR-181c Regulates the process of the Infection of Singapore Grouper Iridovirus via targeting PDCD4 in Epinephelus coioides miR-181c通过靶向石斑鱼体内PDCD4细胞调控新加坡石斑鱼虹膜病毒的感染过程。

IF 2.4 3区农林科学 Q1 FISHERIES

Developmental and comparative immunology

Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.dci.2026.105548

Hong Qi , Jia-Yang He , Jia-Ru Zhou , Yun-Xiang Lin , Yu-Rong Lei, Hai Zhu He, Wei-Yang Huang, Qi-Wei Qin, Hong-Yan Sun

Recent studies found that non-coding RNA could be involved in the development of pathogen infection. In this study, the role of non-coding RNA miRNA-181c (miR-181c) response to Iridovirus SGIV (an important viral pathogen and can cause huge economic losses in marine fish industry) infection was explored in Epinephelus coioides, an important economic fish in South China. The results showed that SGIV infection inhibited the expression of E. coioides miR-181c. Upregulated miR-181c significantly inhibited the invasion of SGIV, the expressions of key SGIV genes (MCP, ICP18, LITAF and VP19), SGIV-induced CPE, and the titers of SGIV. Programmed cell death 4 (PDCD4) of E. coioides was a direct target of miR-181c. miR-181c could regulate the expressions of the immune- and apoptosis-related factors, and SGIV-induced apoptosis via targeting PDCD4. Downregulated miR-181c could produce the opposite results. These findings would be useful for exploring miRNAs for potentially controlling viral infection.

近年来的研究发现，非编码RNA可能参与了病原体感染的发生。本研究探讨了非编码RNA miRNA-181c （miR-181c）在华南重要经济鱼类石斑鱼（Epinephelus coioides）感染虹膜病毒（Iridovirus SGIV）时的应答作用。虹膜病毒是一种重要的病毒病原体，可给海鱼产业造成巨大的经济损失。结果显示，SGIV感染抑制了大肠杆菌miR-181c的表达。上调miR-181c可显著抑制SGIV的侵袭、SGIV关键基因（MCP、ICP18、LITAF和VP19）的表达、SGIV诱导的CPE和SGIV滴度。大肠杆菌的程序性细胞死亡4 （PDCD4）是miR-181c的直接靶点。miR-181c可以通过靶向PDCD4调控免疫和凋亡相关因子的表达，以及sgiv诱导的细胞凋亡。下调miR-181c可能产生相反的结果。这些发现将有助于探索潜在控制病毒感染的mirna。

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引用次数: 0

Impact of viral ribonucleoprotein complex genetic stability on pathogenicity in H9N2 and H6N2 avian influenza viruses 病毒核糖核蛋白复合体遗传稳定性对H9N2和H6N2禽流感病毒致病性的影响

IF 2.4 3区农林科学 Q1 FISHERIES

Developmental and comparative immunology

Pub Date : 2026-02-01 Epub Date: 2025-12-27 DOI: 10.1016/j.dci.2025.105544

Yuwen Luo , Mengyi Dong , Yuxi Shen , Xuelian Xiang , Jiadai Lv , Yi Sun , Yongxin Li , Yamei Huang , Min Cui , Xinfeng Han , Jing Xia , Yong Huang

China has a great demand for poultry, while avian influenza (AI) remains widespread and exhibits high instability, posing a persistent challenge to the poultry industry. Elucidating the genetic stability of avian influenza variants and their implications for pathogenicity is key for pandemic risk mitigation. H9 and H6 AIVs have co-circulated in China due to a specific evolutionary dynamic: H9 AIVs serve as stable genetic reservoirs, whereas H6 AIVs act as platforms for multi-subtype reassortment. This reassortment process continually generates novel variants with unpredictable virulence, posing a persistent biosecurity threat to poultry production. Genetic stability analysis of H9/H6 AI viral Ribonucleoprotein (vRNP) complexes (PB2, PB1, PA, NP) revealed clear subtype-specific divergence. H9 AIVs retained highly conserved gene constellations, whereas H6 AIVs exhibited pronounced plasticity, acquiring 42.5 % of PB2, 20.1 % of PA, and 23.7 % of NP genes from other AIV subtypes. The H9vRNP-H6 reassortant (H6N2 backbone carrying H9N2 vRNP) showed enhanced replicability in both MDCK cells (4.7 → 5.7 log₁₀TCID₅₀/mL) and embryonated eggs (6.7 → 7.7 log₁₀EID₅₀/mL), with significantly promoted pathogenicity in chicks. These findings highlight the urgent need to integrate genetic surveillance of H9 and H6 AIVs into targeted prevention frameworks, thereby forestalling the emergence of pandemic-prone reassortants and mitigating potential losses to the poultry industry and public health. Hence, such research would provide a theoretical basis for the development of novel vaccines and enhance strategies for the control and prevention of avian influenza.

中国对家禽有很大的需求，而禽流感（AI）仍然广泛传播并表现出高度不稳定性，对家禽业构成了持续的挑战。阐明禽流感变异的遗传稳定性及其对致病性的影响是减轻大流行风险的关键。由于特定的进化动态，H9和H6 aiv在中国共传播：H9 aiv作为稳定的遗传库，而H6 aiv作为多亚型重配的平台。这种重组过程不断产生具有不可预测毒性的新变种，对家禽生产构成持续的生物安全威胁。H9/H6 AI病毒核糖核蛋白（vRNP）复合物（PB2, PB1， PA， NP）的遗传稳定性分析显示出明显的亚型特异性差异。H9型AIV保留了高度保守的基因群，而H6型AIV表现出明显的可塑性，从其他AIV亚型获得了42.5%的PB2、20.1%的PA和23.7%的NP基因。H9vRNP-H6重组体（携带H9N2 vRNP的H6N2主干）在MDCK细胞（4.7→5.7 log10TCID50/mL）和胚蛋（6.7→7.7 log10EID50/mL）中的可复制性增强，在雏鸡中的致病性显著提高。这些发现突出表明，迫切需要将H9和H6禽流感病毒的遗传监测整合到有针对性的预防框架中，从而防止出现易于流行的重组，并减轻对家禽业和公共卫生的潜在损失。因此，这种研究将为开发新型疫苗和加强控制和预防禽流感的战略提供理论基础。

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引用次数: 0

Functional characterization of short-isoform of PARP12 in the immune response to SVCV infection in common carp (Cyprinus carpio) 鲤对SVCV感染免疫应答中PARP12短亚型的功能研究

IF 2.4 3区农林科学 Q1 FISHERIES

Developmental and comparative immunology

Pub Date : 2026-02-01 Epub Date: 2026-01-13 DOI: 10.1016/j.dci.2026.105552

Ting Li, Yingying Zhang, Cuixia Wang, Ruikuan Yu, Dongchun Yan, Lingjun Si, Linrui Chang

Poly(ADP-ribose) polymerase 12 (PARP12), which has been identified as an interferon-stimulated gene (ISG), is able to restrict virus replication via PARP-dependent ADP-ribosylation of target molecules. Presently, the antiviral abilities of PARP12 have been reported in mammalian organisms, whereas no data is available on the immune function of PARP12 in fish species. In the present study, a PARP12 gene (CcPARP12) was identified from common carp (Cyprinus carpio), and its role in antiviral immune response was investigated. Structurally, CcPARP12 was shown to consist of ZnF-C3H1 motifs and WWE domain, which was in line with PARP12-short (S) isoform in domain architecture. In vivo gene expression analysis showed that CcPARP12 mRNA expression levels were varied in various tissues of healthy carps with the highest level in head kidney, and spring viraemia of carp virus (SVCV) induced CcPARP12 expression in multiple immune-related tissues. Analysis of subcellular localization showed that CcPARP12 was located in the nucleus region of EPC cells. Additionally, in vitro, it was shown that CcPARP12 could affect SVCV replication in EPC cells, with reduced virus load and relieved cytopathic effects (CPEs), and moreover positively regulated the expressions of antiviral molecules ISG15, IFN and Viperin in response to SVCV infection. Overall, these results indicated that CcPARP12 could play the defensive role in the host immune response to SVCV infection. This study has broadened the understanding of antiviral properties of PARP12 in fish species and even lower vertebrates, providing potential new therapeutic targets against SVCV infection.

聚（adp -核糖）聚合酶12 （PARP12）已被确定为干扰素刺激基因（ISG），能够通过parp依赖性靶分子的adp核糖基化来限制病毒复制。目前，PARP12在哺乳动物体内的抗病毒能力已被报道，而PARP12在鱼类体内的免疫功能尚无相关数据。本研究从鲤鱼（Cyprinus carpio）中鉴定出一个PARP12基因（CcPARP12），并对其在抗病毒免疫应答中的作用进行了研究。在结构上，CcPARP12由ZnF-C3H1基序和WWE结构域组成，在结构域结构上符合PARP12-short (S)亚型。体内基因表达分析表明，CcPARP12 mRNA在健康鲤鱼各组织中表达水平存在差异，其中头肾表达水平最高，鲤病毒春季病毒血症（SVCV）诱导CcPARP12在多种免疫相关组织中表达。亚细胞定位分析表明，CcPARP12位于EPC细胞的核区。此外，体外实验表明，CcPARP12能够影响SVCV在EPC细胞中的复制，降低病毒载量，减轻细胞病变效应（cpe），并积极调节抗病毒分子ISG15、IFN和Viperin的表达，以应对SVCV感染。综上所述，这些结果表明CcPARP12可能在宿主对SVCV感染的免疫应答中发挥防御作用。该研究拓宽了对PARP12在鱼类甚至低等脊椎动物中的抗病毒特性的认识，为抗SVCV感染提供了潜在的新治疗靶点。

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引用次数: 0

Identification and functional characterization of a circular RNA circeIF4G3: a negative regulator of innate immunity in miiuy croaker (Miichthys miiuy) 环状RNA circeIF4G3的鉴定和功能表征：小斑马鱼先天免疫负调节因子。

IF 2.4 3区农林科学 Q1 FISHERIES

Developmental and comparative immunology

Pub Date : 2026-01-01 Epub Date: 2025-12-03 DOI: 10.1016/j.dci.2025.105537

Yanqiu Cui , Yaqi Tao , Tianjun Xu , Yuena Sun

In recent years, the unique circular structure of circular RNAs (circRNAs) has been the focus of much attention and research. RNA molecules without coding function weave a complex regulatory network in mammals, affecting the progress of many biological processes. This discovery opens up a new perspective on the function of the genome. However, the powerful regulatory functions of circular RNAs in fish are still unclear. We identified a novel circular RNA, dubbing it circeIF4G3. Through qPCR and dual luciferase assays, we found that circeIF4G3 reduces the production of antiviral genes and inflammatory factors. We discovered that circeIF4G3 both hindered cell proliferation and diminished cell viability concurrently. These results suggest that circeIF4G3 is not only involved in the innate immunity of miiuy croaker, but also plays an inhibitory role in it. This discovery provides a new research approach for a deeper understanding of the immune regulatory mechanism of miiuy croaker. This study enriches the non-coding RNAs regulatory network in innate immunity in teleost fish, and establishes a foundation for investigating the role of circular RNAs in teleost fish's innate immunity.

近年来，环状rna （circRNAs）独特的环状结构一直是人们关注和研究的焦点。没有编码功能的RNA分子在哺乳动物体内编织了一个复杂的调控网络，影响着许多生物过程的进展。这一发现开辟了研究基因组功能的新视角。然而，环状rna在鱼类中的强大调控功能尚不清楚。我们发现了一种新的环状RNA，将其命名为circeIF4G3。通过qPCR和双荧光素酶检测，我们发现circeIF4G3可以减少抗病毒基因和炎症因子的产生。我们发现circeIF4G3同时抑制细胞增殖和降低细胞活力。这些结果表明circeIF4G3不仅参与黄花鱼的先天免疫，而且在其中发挥抑制作用。这一发现为深入了解黄花鱼免疫调节机制提供了新的研究途径。本研究丰富了硬骨鱼先天免疫的非编码rna调控网络，为探讨环状rna在硬骨鱼先天免疫中的作用奠定了基础。

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引用次数: 0

The VIP-VIPR2 axis strengthens intestinal barrier integrity and antimicrobial immunity in Ctenopharyngodon idella VIP-VIPR2轴增强海蛇肠道屏障完整性和抗菌免疫。

IF 2.4 3区农林科学 Q1 FISHERIES

Developmental and comparative immunology

Pub Date : 2026-01-01 Epub Date: 2025-12-16 DOI: 10.1016/j.dci.2025.105539

Xiaofeng Liu , Qian Hou , Zejun Zhou

Bacterial pathogens like Aeromonas hydrophila threaten aquaculture by compromising fish immune defenses. The intestinal barrier is a critical frontline defense against pathogenic bacteria in fish, yet its regulation by neuroimmune mechanisms remains poorly understood. In this study, we investigated the role of vasoactive intestinal peptide (VIP) in the immune response of grass carp (Ctenopharyngodon idella) following bacterial challenge. The full-length grass carp VIP gene was 462 bp, encoding a 153-amino acid precursor protein with high sequence conservation across vertebrates. VIP expression was highest in the intestinal tract and significantly upregulated upon A. hydrophila infection. Administration of recombinant grass carp VIP protein enhanced intestinal barrier function by increasing the expression of tight junction molecules (ZO-1, Occludin, Claudin-1) and the immunoregulatory cytokine IL-22, while reducing plasma LPS and D-lactate levels. Furthermore, grass carp VIP treatment promoted the expression of the mucosal barrier component MUC2 and antimicrobial peptides (LEAP-2, Lyz1, Hepcidin-1), reduced bacterial load, and significantly improved survival rates. Mechanistic studies confirmed that VIP interacted specifically with the VIP receptor 2 (VIPR2), and knockdown of VIPR2 abolished the protective effects of VIP on barrier integrity and antimicrobial immunity. These findings demonstrate that the VIP-VIPR2 axis plays a crucial role in modulating intestinal immunity in grass carp, offering new insights into neuroimmune regulation in aquatic animals during pathogenic challenge.

细菌性病原体如嗜水气单胞菌通过损害鱼类的免疫防御威胁水产养殖。肠道屏障是鱼类对抗致病菌的关键一线防御，但其在神经免疫机制中的调节作用仍知之甚少。在本研究中，我们研究了血管活性肠肽（VIP）在草鱼（Ctenopharyngodon idella）细菌攻击后免疫反应中的作用。草鱼VIP基因全长462 bp，编码一个含有153个氨基酸的前体蛋白，在脊椎动物中具有高度的序列保守性。VIP的表达在肠道中最高，在嗜水单胞菌感染时显著上调。重组草鱼VIP蛋白通过增加紧密连接分子（ZO-1、Occludin、Claudin-1）和免疫调节细胞因子IL-22的表达，同时降低血浆LPS和d -乳酸水平，增强了肠道屏障功能。此外，VIP处理促进了草鱼粘膜屏障组分MUC2和抗菌肽（LEAP-2、Lyz1、Hepcidin-1）的表达，降低了细菌负荷，显著提高了草鱼存活率。机制研究证实VIP与VIP受体2 （VIPR2）特异性相互作用，VIPR2的敲低可消除VIP对屏障完整性和抗菌免疫的保护作用。这些研究结果表明，VIP-VIPR2轴在草鱼肠道免疫调节中起着至关重要的作用，为水生动物在病原攻击期间的神经免疫调节提供了新的见解。

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引用次数: 0

Dynamic remodeling of gut microbiota and untargeted etabolomics in Sebastes schlegelii during Edwardsiella piscicida infection 鱼毒爱德华菌感染期间施莱格氏塞巴斯菌肠道菌群的动态重塑和非靶向代谢组学研究

IF 2.4 3区农林科学 Q1 FISHERIES

Developmental and comparative immunology

Pub Date : 2026-01-01 Epub Date: 2025-12-05 DOI: 10.1016/j.dci.2025.105534

Xiantong Liu , Ruixue Wu , Ning Ning Wang , Hua Xu , Xiaojun Rong , Chao Li , Min Cao

The intestinal microbiota is a critical mediator of host immune responses and metabolic homeostasis, especially during the pathogenic challenge. This study investigated the dynamic remodeling of the gut microbiota and metabolome in Sebastes schlegelii following infection with the major aquaculture pathogen Edwardsiella piscicida. Using 16S rRNA gene sequencing and untargeted metabolomics, we analyzed the microbial community composition and metabolic profiles of intestinal samples at multiple time points post-infection. Our results revealed significant temporal shifts in bacterial diversity and structure. Notably, the abundances of genera such as Bacteroides, Bacillus, and Lactobacillus increased, while Comamonas and Cutibacterium decreased. Metabolomic analysis identified 1063 metabolites, with lipids and lipid-like molecules being the most abundant. Differential analysis revealed stage-specific metabolic alterations: early infection was marked by the upregulation of pro-inflammatory mediators such as lithocholic acid and palmitoylethanolamide, whereas late infection featured elevated levels of anti-inflammatory metabolites, including cholic acid and agmatine. KEGG pathway analysis indicated an initial enrichment in general metabolic processes, followed by a shift to steroid biosynthesis later in the infection. These findings suggest a coordinated “metabolic switch" mechanism that modulates inflammation and promotes recovery. This study provides novel insights into the microbiota–metabolite–immune network in S. schlegelii and highlights potential biomarkers for monitoring fish health status in aquaculture.

肠道微生物群是宿主免疫反应和代谢稳态的重要介质，特别是在致病性挑战期间。本研究研究了schlegelsebas在感染主要水产养殖病原体鱼毒爱德华菌（Edwardsiella piscicida）后肠道微生物群和代谢组的动态重塑。利用16S rRNA基因测序和非靶向代谢组学，我们分析了感染后多个时间点肠道样本的微生物群落组成和代谢谱。我们的研究结果揭示了细菌多样性和结构的显著时间变化。值得注意的是，拟杆菌属（Bacteroides）、芽孢杆菌属（Bacillus）和乳杆菌属（Lactobacillus）的丰度增加，而单胞菌属（Comamonas）和表皮杆菌属（Cutibacterium）的丰度减少。代谢组学分析鉴定出1063种代谢物，其中脂质和类脂分子最为丰富。差异分析揭示了特定阶段的代谢改变：早期感染的特点是促炎介质如石胆酸和棕榈酰乙醇酰胺的上调，而晚期感染的特点是抗炎代谢物水平升高，包括胆酸和胍丁胺。KEGG通路分析表明，在一般代谢过程中初始富集，随后在感染后期转向类固醇生物合成。这些发现表明了一种协调的“代谢开关”机制，可以调节炎症并促进恢复。该研究为schlegelii的微生物群-代谢物-免疫网络提供了新的见解，并强调了在水产养殖中监测鱼类健康状况的潜在生物标志物。

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引用次数: 0

Transcriptomic analysis reveals the immune-related function of miR-122 in Larimichthys crocea 转录组学分析揭示了miR-122在鳜鱼中的免疫相关功能。

IF 2.4 3区农林科学 Q1 FISHERIES

Developmental and comparative immunology

Pub Date : 2026-01-01 Epub Date: 2025-12-23 DOI: 10.1016/j.dci.2025.105541

Lifang Wen , Sisi Wei , Li Wu , Zhenqi Xin , Mingshan Song , Weifeng Wang , Baoying Guo

引用次数: 0

Hypoxia impairs monocyte/macrophage function and host defense via ALAS2-mediated heme biosynthesis in Japanese sea bass (Lateolabrax japonicus) 缺氧通过alas2介导的日本黑鲈血红素生物合成损害单核/巨噬细胞功能和宿主防御

IF 2.4 3区农林科学 Q1 FISHERIES

Developmental and comparative immunology

Pub Date : 2026-01-01 Epub Date: 2025-12-15 DOI: 10.1016/j.dci.2025.105538

Wei-Wei Fang , Yi-Xin Wu , Yi-Bin Cao , Xin-Jiang Lu , Jian-Rao Hu

Hypoxia compromises host defense in fish by impairing macrophage function, but the underlying mechanisms remain unclear. This study elucidates the molecular mechanisms by which hypoxia disrupts monocytes/macrophages (MO/MФ) function in Japanese sea bass (Lateolabrax japonicus), with a particular focus on the regulatory role of heme biosynthesis and its key gene, 5′-aminolevulinate synthase 2 (ALAS2). Phylogenetic analysis confirmed high evolutionary conservation of ALAS2 across vertebrates, supporting its fundamental role in heme metabolism. Transcriptomic analysis revealed that hypoxia induced the upregulation of genes involved in heme biosynthesis of MO/MФ, particularly ALAS2. Functional assays demonstrated that heme accumulation under hypoxic conditions impaired MO/MФ phagocytic and bactericidal activities, while also promoted the production of pro-inflammatory cytokines. These dysfunctions were mediated by the ALAS2-heme signaling axis, which orchestrated inflammatory responses and metabolic reprogramming throughout the study. Knockdown of ALAS2 enhanced phagocytic activity and suppressed pro-inflammatory cytokine expression, suggesting its critical role in modulating MO/MФ function under hypoxia. Furthermore, inhibition of heme synthesis improved fish survival rates and reduced bacterial burdens during Vibrio harveyi infection. These findings elucidate the pivotal role of heme in regulating MO/MФ function and host defense under hypoxic conditions, providing mechanistic insights into hypoxia-induced immune suppression in aquaculture.

缺氧通过损害巨噬细胞功能来损害鱼类的宿主防御，但潜在的机制尚不清楚。本研究阐明了缺氧破坏日本黑鲈（Lateolabrax japonicus）单核/巨噬细胞（MO/MФ）功能的分子机制，重点研究了血红素生物合成及其关键基因5′-氨基乙酰酸合成酶2 （ALAS2）的调控作用。系统发育分析证实了ALAS2在脊椎动物中的高度进化保守性，支持其在血红素代谢中的基本作用。转录组学分析显示，缺氧诱导MO/MФ血红素生物合成相关基因上调，尤其是ALAS2。功能分析表明，缺氧条件下血红素的积累损害了MO/MФ的吞噬和杀菌活性，同时也促进了促炎细胞因子的产生。这些功能障碍是由alas2 -血红素信号轴介导的，在整个研究过程中，它协调了炎症反应和代谢重编程。敲低ALAS2可增强吞噬活性，抑制促炎细胞因子表达，提示其在缺氧条件下调节MO/MФ功能中起关键作用。此外，抑制血红素合成提高了鱼的存活率，并减少了感染哈维弧菌时的细菌负担。这些发现阐明了血红素在缺氧条件下调节MO/MФ功能和宿主防御中的关键作用，为缺氧诱导的水产养殖免疫抑制提供了机制见解。

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