Fish & shellfish immunology最新文献

{"title":"Development of a CD3ε mAb that can identify and in vitro activate T cells in large yellow croaker (Larimichthys crocea)","authors":"Zhichao Fang ,&nbsp;Yi Cao ,&nbsp;Haokai Chen ,&nbsp;Jie Cheng ,&nbsp;Ming Geng ,&nbsp;Jiong Chen ,&nbsp;Yinnan Mu ,&nbsp;Kang Li ,&nbsp;Jialong Yang ,&nbsp;Xiumei Wei","doi":"10.1016/j.fsi.2025.110461","DOIUrl":"10.1016/j.fsi.2025.110461","url":null,"abstract":"<div><div>As a hallmark molecule of T cells, CD3ε forms a complex with T-cell receptor (TCR) to transduce antigen signals and drive T cell activation, playing a pivotal role in T cell-mediated immune response. However, the lack of specific monoclonal antibodies (mAbs) targeting CD3ε in fish has substantially impeded the study on adaptive immunity in these species. In this study, we constructed NIH/3T3 cells expressing CD3ε of the large yellow croaker (<em>Larimichthys crocea</em>) via retroviral transduction. Using these cells as immunogen to immune mice, we generated a mAb that specifically recognized a population of spleen leukocytes after cell fusion and screening. This identified population specifically expressed CD3ε, CD4-1 or CD8α, suggesting that it was T cell. Moreover, immunofluorescence demonstrated that the mAb could bind to the surface of some leukocytes, and it was detected as the IgG1 type. These results confirmed the specificity of this CD3ε mAb and its applicability to identify T cells in the large yellow croaker. Subsequently, we revealed the widespread distribution of CD3ε⁺ T cells in immune-related tissues including spleen, liver, head kidney, gill and peripheral blood by using this mAb. Upon PHA stimulation, the phosphorylation of mTORC1 and MAPK/ERK were enhanced in CD3ε⁺ T cells. More importantly, this CD3ε mAb could mimic antigenic signaling to induce T cell activation <em>in vitro</em>, since its treatment activated the mTORC1, MAPK/ERK and Ca²⁺ pathways which were crucial for T cell activation. Therefore, we generated a CD3ε mAb, which could not only identify but also <em>in vitro</em> activate T cells of the large yellow croaker, providing critical tools for investigating T-cell immune in teleost.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"165 ","pages":"Article 110461"},"PeriodicalIF":4.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigallocatechin gallate (EGCG) inhibits Micropterus salmoides rhabdovirus replication via suppressing viral attachment and infectivity","authors":"Yuhang Wang ,&nbsp;Shuangshuang Mao ,&nbsp;Xiaoran Feng ,&nbsp;Reng Qiu ,&nbsp;Na Li ,&nbsp;Lunguang Yao ,&nbsp;Yinghui Qin","doi":"10.1016/j.fsi.2025.110467","DOIUrl":"10.1016/j.fsi.2025.110467","url":null,"abstract":"<div><div><em>Micropterus salmoides</em> rhabdovirus (MSRV) remains an economically important pathogen in the global largemouth bass industry, effective drugs to control the virus are still lacking. Epigallocatechin gallate (EGCG), the most abundant and bioactive catechin in green tea, possesses multiple biological activities, including widespread antiviral effects. However, whether EGCG can inhibit MSRV infection remains unknown. Here, we tried to determine the role of EGCG in MSRV replication and to investigate its underlying mechanisms. Cell viability and drug treatment assays showed that EGCG significantly inhibited MSRV replication at the concentration range of 1–40 μM without obvious cytotoxicity. Pretreatment assay indicated that treating EPC cells with EGCG before MSRV infection has no significant inhibition on MSRV replication, suggesting the antiviral action of EGCG might not target to MSRV receptor and/or related proteins required for MSRV infection. Time of addition assays indicated that EGCG exerted antiviral activity in the early stage of MSRV life cycle. Further studies showed that EGCG possesses excellent inhibitory effects on the attachment step of MSRV. The virucidal assay revealed EGCG directly attenuated MSRV infectivity, which may partly account for its anti-MSRV effect. In vivo experiments showed that EGCG improved the survival rate of MSRV-challenged fish by 21 %. Altogether, EGCG exhibited a strong anti-MSRV activity and might be a promising therapeutic drug for MSRV infection.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"165 ","pages":"Article 110467"},"PeriodicalIF":4.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular cloning, expression, and functional analysis of cystatin B from silver pomfret (Pampus argenteus) under Vibrio parahaemolyticus challenge","authors":"Yadong Xue ,&nbsp;Dianyang Zhou ,&nbsp;Zhennan Sun ,&nbsp;Xiumei Liu ,&nbsp;Yajun Wang ,&nbsp;Suming Zhou ,&nbsp;Xubo Wang","doi":"10.1016/j.fsi.2025.110465","DOIUrl":"10.1016/j.fsi.2025.110465","url":null,"abstract":"<div><div>Cystatin B is an intracellular inhibitor that regulates the activity of cysteine proteases. In this study, the coding sequence of silver pomfret <em>cystatin B</em> was successfully cloned and identified, which was 297 bp in length, predicted to encode 98 amino acids with a molecular weight of approximately 11.12 kDa. Sequence analysis revealed that PaCystatin B (<em>Pampus argenteus</em> Cystatin B) exhibited a high degree of conservation with Cystatin B orthologs from other fish species, maintaining characteristic motifs essential for cysteine protease inhibition, such as the conserved QXVXG motif. Tissue distribution analysis indicated that <em>Pacystatin B</em> was highly expressed in the gills and head kidney, with relatively lower expression levels observed in the liver. Additionally, following <em>Vibrio parahaemolyticus</em> challenge, the expression levels of <em>Pacystatin B</em> were significantly upregulated in the trunk kidney and liver, contrasted with marked downregulation in the gills, reflecting the distinct response strategies of different tissues in silver pomfret against pathogenic infection. Functional characterization demonstrated that the recombinant PaCystatin B (rPaCystatin B) not only exhibited pronounced inhibitory activity against cysteine proteases but also showed significant antibacterial effects against several pathogenic bacteria, including <em>Staphylococcus aureus</em>, <em>Escherichia coli</em>, <em>Vibrio parahaemolyticus</em>, and <em>Edwardsiella tarda</em>. Notably, the antibacterial efficacy of PaCystatin B remained stable even after short-term exposure to high temperatures. In conclusion, these findings suggested that <em>Pacystatin B</em> might play a critical role in the immune response of silver pomfret against pathogen invasion, thereby providing new insights into the immunological mechanisms of cystatins in teleosts.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"165 ","pages":"Article 110465"},"PeriodicalIF":4.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atlantic salmon scale explants in bacteria-host interaction studies: in vitro challenge model","authors":"Aleksei Krasnov ,&nbsp;Amritha Johny ,&nbsp;Elisabeth Ytteborg ,&nbsp;Sergey Afanasyev ,&nbsp;Marianne H. Selander Hansen ,&nbsp;Marianne Vaadal ,&nbsp;Christian Karlsen","doi":"10.1016/j.fsi.2025.110466","DOIUrl":"10.1016/j.fsi.2025.110466","url":null,"abstract":"<div><div>Cell lines and primary cultures are widely used to study host-pathogen interactions, reducing the need for challenge trials with live fish, which are costly and raise ethical concerns. We present Atlantic salmon scale explants (SE) as a promising model for bacterial challenges. Comparison with the body map (transcriptomes of seventeen cells and tissues) revealed strong immune activity in SE. SE ranked first in antiviral gene expression and second and third in antibacterial and inflammatory responses, respectively. Additionally, SE shows high expression of skin-specific genes encoding structural proteins of the cytoskeleton and extracellular matrix. Contrast to the epidermis, dermis, and whole skin highlights immune genes, including markers of acute inflammation and stress. Exposure to pathogens (<em>Moritella viscosa</em> and <em>Tenacibaculum finnmarkense</em>) and commensal bacteria consistently upregulated a suite of immune genes in a dose response manner. This panel includes chemokines, cytokines, genes involved in eicosanoid metabolism, and both humoral and cellular effectors. The prevalence of genes related to signaling and communication suggests that salmon scales function as sentinels, mobilizing immune responses upon encountering bacteria. While common immune responses were evident across all trials, scales also revealed differences between bacterial species. Combining commensal bacteria with <em>M. viscosa</em> enhanced responses to pathogens, and differences were observed between <em>M. viscosa</em> and <em>T. finnmarkense</em>. The effects of commensal bacteria varied in magnitude. Exposed cells showed changes in morphology and increased iNOS expression. Future development of this model will focus on time-course experiments and expanding the analytical repertoire to include pathology detection methods.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"165 ","pages":"Article 110466"},"PeriodicalIF":4.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of interferon regulatory factor 8 (IRF8) in Nile tilapia (Oreochromis niloticus)","authors":"Huaqing Sun ,&nbsp;Chao Li ,&nbsp;Yang Lei ,&nbsp;Yujie Wang ,&nbsp;Bingxi Li ,&nbsp;Jianmin Ye","doi":"10.1016/j.fsi.2025.110426","DOIUrl":"10.1016/j.fsi.2025.110426","url":null,"abstract":"<div><div>Interferon regulatory factor 8 (IRF8) participates in the defense against pathogens. In this study, we cloned and characterized <em>OnIRF8</em> from Nile tilapia (<em>Oreochromis niloticus</em>) and investigating its immune response functions both <em>in vivo</em> and <em>in vitro</em>. The encoded open reading frame comprises of 420 amino acids, with a predicted molecular weight of 47.645 kDa. It exhibits a high degree of sequence homology (ranging from 50.57 % to 98.81 %) with IRF8 orthologs from other vertebrates. Ubiquitous OnIRF8 expression was detected across tissues, with the highest expression observed in the spleen. Both <em>in vivo</em> and <em>in vitro</em> analyses revealed that the transcription levels of <em>OnIRF8</em> were significantly up-regulated in response to treatments with <em>Streptococcus agalactiae</em>, <em>Aeromonas hydrophila</em>, Lipopolysaccharide (LPS) and polyinosinic acid:polycytidylic acid (poly (I:C)) in the head kidney and spleen. Furthermore, overexpression of <em>OnIRF8</em> in Nile tilapia significantly enhanced immune-related gene expression in head kidney monocytes/macrophages. Overexpression of <em>OnIRF8</em> also reduced bacterial load in head kidney and spleen post-<em>S. agalactiae</em> infection, with up-regulation of inflammatory factor production. OnIFN-<em>γ</em> recombinant protein and poly (I:C) could both markedly amplified <em>OnIRF8</em> expression, implying its potential dual role in modulating both OnIFN-<em>γ</em> and TLR signaling pathways. These findings indicate that OnIRF8 may serve a protective function against bacterial infections and act as an immunomodulatory factor in Nile tilapia.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"165 ","pages":"Article 110426"},"PeriodicalIF":4.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome analysis of medaka spermatogonial stem cell line (SG3) infected with ranaviruses in vitro","authors":"Linwen Cheng ,&nbsp;Shiwen Zhang ,&nbsp;Zhongyi Liu ,&nbsp;Qiqi Jiang ,&nbsp;Mingyou Li ,&nbsp;Fei Ke ,&nbsp;Lang Gui","doi":"10.1016/j.fsi.2025.110453","DOIUrl":"10.1016/j.fsi.2025.110453","url":null,"abstract":"<div><div>The medaka spermatogonial stem cell line (SG3) is a well-established cell line that can be induced to differentiate into sperm <em>in vitro</em>. <em>Ranavirus</em>, a genus of viruses widely distributed among fish, amphibians, and reptiles, poses a significant threat to these organisms. This study aimed to investigate the morphological changes and transcriptomic responses in SG3 following infection with three ranavirus strains: <em>Andrias davidianus</em> ranavirus (ADRV), <em>Rana grylio</em> virus (RGV), and <em>Siniperca chuatsi</em> ranavirus (SCRaV). Microscopic observations confirmed that SG3 cells were susceptible to all three ranaviruses, resulting in cellular swelling and membrane rupture, with infection confirmed through Real-time PCR. Transcriptomic profiling identified conserved responses: downregulation of early growth response protein (<em>Egr1</em>) and upregulation of myelocytomatosis oncogene (<em>MYC</em>). Ranavirus infection elevated alternative splicing events, with skipped exon events dominated and the maximal divergence observed at the 12 h post-infection. Key cellular metabolic pathways including glycolysis were disrupted, marked by coordinated upregulation of glycolytic enzymes and suppression of gluconeogenic enzymes. These results elucidate conserved molecular strategies underlying ranavirus-host interactions and metabolic mechanisms.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"165 ","pages":"Article 110453"},"PeriodicalIF":4.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mini-review on cathelicidin in fish: Gene expression, immune function, and evolutionary insights","authors":"Meihua Zhu ,&nbsp;Yan Yang ,&nbsp;Bei Huang ,&nbsp;Wenshu Huang","doi":"10.1016/j.fsi.2025.110463","DOIUrl":"10.1016/j.fsi.2025.110463","url":null,"abstract":"<div><div>Cathelicidins are a family of cationic antimicrobial peptides that play a critical role in innate immune defense. Like other antimicrobial peptides, cathelicidins can effectively kill pathogens while minimizing the risk of promoting antimicrobial resistance, a growing concern in the aquaculture. Although cathelicidins are widely distributed across vertebrates, from basal vertebrate species such as hagfish and lampreys to mammals, the number of identified cathelicidin sequences in fish remains relatively limited. This review aims to provide a comprehensively summary of current knowledge on teleost cathelicidins, focusing on their expression patterns, antimicrobial activity, and immunomodulatory functions, while also outlining future research directions. Additionally, we conducted a genomic analysis to explore the species distribution and evolutionary history of fish cathelicidins. Our results revealed conserved synteny of cathelicidin loci in both cartilaginous and bony fishes, as well as lineage-specific expansions and chromosomal rearrangements that may have contributed to gene loss. Overall, this study serves as valuable resource for understanding cathelicidins in fish, and lays the groundwork for future investigations into their evolution, biological functions, and potential applications in fish health and aquaculture.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"165 ","pages":"Article 110463"},"PeriodicalIF":4.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydromyricetin switches pyroptosis to apoptosis during Aeromonas hydrophila infection in Mylopharyngodon piceus","authors":"Jingjing Xu ,&nbsp;Can Yang ,&nbsp;Jing Xiang ,&nbsp;Rui Song ,&nbsp;Dongsheng Ou ,&nbsp;Ruozhong Wang","doi":"10.1016/j.fsi.2025.110460","DOIUrl":"10.1016/j.fsi.2025.110460","url":null,"abstract":"<div><div><em>Ampelopsis grossedentata</em> is a traditional Chinese medicine used to treat fever, anti-inflammatory and parasitic infections. Dihydromyricetin is one of the flavonoids with high content, which has been proved to have certain antibacterial and anti-inflammatory effects. However, its antibacterial mechanism is still unclear. In this study, the mechanisms by which <em>A</em>. <em>grossedentata</em> extract and dihydromyricetin promote the organism's defence against <em>A. hydrophila</em> were investigated. The results showed that both <em>A</em>. <em>grossedentata</em> grape extract and dihydromyricetin (DMY) promoted the expression of IL1β in MPK cells. <em>A. hydrophila</em> infection resulted in a significant increase in the expression of caspase1, IL1β, and GSDME, and a significant enhancement of IL1β and LDH release, which were slowed down by DMY. Differently, on the basis of the up-regulation of <em>A. hydrophila</em>, DMY treatment further enhanced the expression of caspase3 and BAX and the activity of caspase3 resulting in stronger apoptosis. And at the same time, the titer of <em>A. hydrophila</em> was decreased by DMY treatment. In black carp (<em>Mylopharyngodon piceus</em>), injections of <em>A</em>. <em>grossedentata</em> extract and DMY also significantly reduced the lethality of <em>A. hydrophila</em>. The up-regulation of the expression of genes associated with pyroptosis due to <em>A. hydrophila</em> infection in splenocytes was attenuated by dihydromyricetin treatment, whereas the expression of apoptosis-associated genes was significantly enhanced. Tissue sections showed significant damage to splenic tissue following <em>A. hydrophila</em> infection, whereas splenic damage was alleviated and its apoptosis-associated DNA breaks were enhanced by dihydromyricetin injection. DMY may regulate multiple modes of cell death in cells. Further studies revealed that TBK1 may be a molecular target of DMY because of their high structural binding potential and as well as functional synergy and relevance. Therefore, these data implied that DMY potentially regulates TBK1 to transform <em>A. hydrophila</em>-induced pyroptosis into apoptosis. This provides a theoretical basis for the application of dihydromyricetin as an antibiotic alternative and feed additive in aquaculture.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"165 ","pages":"Article 110460"},"PeriodicalIF":4.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the chromatin-driven transcription regulatory networks response to Streptococcus agalactiae infection under low temperature in Nile tilapia","authors":"Songqian Huang ,&nbsp;Wenxin Zhao ,&nbsp;Chenyu Yan ,&nbsp;Jingting Qi ,&nbsp;Xiaolong Li ,&nbsp;Zhichao Wu ,&nbsp;Jiulin Chan ,&nbsp;Liangbiao Chen ,&nbsp;Peng Hu","doi":"10.1016/j.fsi.2025.110464","DOIUrl":"10.1016/j.fsi.2025.110464","url":null,"abstract":"<div><div>Low temperature impairs immune function in ectothermic vertebrates, but the underlying regulatory mechanisms remain unclear. Here, we show that hypothermia significantly decreases bacterial load and increases mortality in Nile tilapia (<em>Oreochromis niloticus</em>) following <em>Streptococcus agalactiae</em> infection. Integrative RNA-seq and ATAC-seq profiling of head kidney tissue revealed widespread suppression of immune gene expression under cold stress, including <em>ifrd2</em>, <em>isg15</em>, <em>cxcr1</em>, <em>ccr2</em>, <em>ccr9a</em>, and <em>socs1b</em>. Footprinting analysis of 259 transcription factor binding elements in accessible chromatin enabled the construction of a transcriptional regulatory network. Cold exposure reduced chromatin accessibility at immune-related transcription factors, including Irf1, Irf3, Irf4, and JunB, thereby dampening downstream gene activation. Irf1 emerged as a key regulator, coordinating the expression of interferon-responsive genes critical for antibacterial defense. Our findings uncover a chromatin-based mechanism of cold-induced immunosuppression in fish, highlighting Irf1-dependent regulatory control as a potential target for enhancing disease resistance under thermal stress.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"164 ","pages":"Article 110464"},"PeriodicalIF":4.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aeromonas hydrophila effector Hcp1 triggers ferroptosis in teleost splenic macrophages via NCOA4-mediated ferritinophagy","authors":"Hao Sun ,&nbsp;Jingqi Ren ,&nbsp;Xiaoyu Ma ,&nbsp;Xinyan Wang ,&nbsp;Anying Zhang ,&nbsp;Hong Zhou","doi":"10.1016/j.fsi.2025.110459","DOIUrl":"10.1016/j.fsi.2025.110459","url":null,"abstract":"<div><div>The fish pathogenic bacterium <em>Aeromonas hydrophila</em> has been proved to trigger ferroptosis in grass carp splenic macrophages mainly via its secreted effectors, but the specific effectors involved remain unclear. In this study, recombinant proteins of several secretory effectors of <em>A. hydrophila</em> were prepared to detect their lipid peroxidation ability in grass carp splenic macrophages, showing that hemolysin coregulated protein 1 (Hcp1) could elevate lipid reactive oxygen species (ROS) production, and the role of Hcp1 in the bacterium-induced ferroptosis was reinforced by using a hcp1-deficient strain of <em>A. hydrophila</em>. Mechanistically, Hcp1 showed great potential to induce iron overload through a dual increase in cytosolic free Fe²⁺ based on ferritin degradation by nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and ferroportin 1 (FPN1) ubiquitination. Moreover, Hcp1 also disturbed GSH/GPX4 antioxidant system by stimulating mitochondrial ROS production to deplete the cellular GSH, which was also driven by NCOA4-mediated ferritinophagy, ultimately impeding lipid ROS scavenging. These multiple effects of Hcp1 underlined its prominent role in <em>A. hydrophila</em>-induced ferroptosis in teleost. Collectively, Hcp1 is a potential effector to elicit ferroptosis via NCOA4-mediated ferritinophagy in teleost, providing a new insight into the pathogenic mechanism of <em>A. hydrophila</em>.</div></div>","PeriodicalId":12127,"journal":{"name":"Fish & shellfish immunology","volume":"164 ","pages":"Article 110459"},"PeriodicalIF":4.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}