{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:24:08Z","timestamp":1780503848553,"version":"3.54.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U22A20536"],"award-info":[{"award-number":["U22A20536"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2025A1515011419"],"award-info":[{"award-number":["2025A1515011419"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shantou University Scientific Research Initiation","award":["NTF25021T"],"award-info":[{"award-number":["NTF25021T"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute hepatopancreatic necrosis disease (AHPND) is one of the most severe threats to global shrimp aquaculture. Recent studies report a significant reduction in hepatopancreas hemocyanin levels in Penaeus vannamei (PvHMC) by AHPND. To investigate the functional implications, we performed liquid chromatography-tandem mass spectrometry\u2013based metabolomics and found that PvHMC knockdown caused a marked accumulation of phosphatidylcholine (PC). qPCR and ELISA analyses further showed that PvHMC suppression upregulated the mRNA expression, protein abundance, and enzymatic activity of PvCPT1, a key enzyme in PC synthesis. Co-immunoprecipitation and confocal immunofluorescence analyses confirmed a direct interaction between PvHMC and PvCPT1, indicating that PvHMC regulates PC metabolism by binding to PvCPT1. Functional assays demonstrated that exogenous PC supplementation significantly increased reactive oxygen species (ROS) production, whereas simultaneous knockdown of PvHMC and PvCPT1 reduced plasma PC levels and ROS activity. Under pathogenic challenge, PC administration inhibited Vibrio parahaemolyticus (VpAHPND) proliferation by enhancing intracellular ROS-mediated antimicrobial responses, ultimately improving shrimp survival. In summary, PvHMC regulates PC metabolism to modulate ROS levels, strengthening shrimp\u2019s immune defense against pathogenic infections. These findings reveal a novel metabolic regulatory role of PvHMC in response to VpAHPND infection and suggest potential strategies for controlling AHPND in shrimp aquaculture.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag018","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T09:55:59Z","timestamp":1773827759000},"source":"Crossref","is-referenced-by-count":1,"title":["Hemocyanin regulates phosphatidylcholine metabolism to enhance reactive oxygen species\u2013mediated immunity in Pacific white shrimp (\n                    <i>Penaeus vannamei<\/i>\n                    )"],"prefix":"10.1093","volume":"215","author":[{"given":"Yunyu","family":"Shi","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Sciences, Shantou University , Shantou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Hui","family":"Kong","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Sciences, Shantou University , Shantou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyuan","family":"Bao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Sciences, Shantou University , Shantou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Sciences, Shantou University , Shantou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Sciences, Shantou University , Shantou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Sciences, Shantou University , Shantou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Guangxi Academy of Fishery Sciences, Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture , Nanning,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1485-0407","authenticated-orcid":false,"given":"Xianliang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Sciences, Shantou University , Shantou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Sciences, Shantou University , Shantou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"2026052212174345900_vkag018-B1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1023\/A:1007054601256","article-title":"Phosphatidylcholine metabolism in human endothelial cells: modulation by phosphocholine","volume":"207","author":"Wong","year":"2000","journal-title":"Mol Cell Biochem"},{"key":"2026052212174345900_vkag018-B2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/s41467-024-55673-1","article-title":"Structural basis for catalysis and selectivity of phospholipid synthesis by eukaryotic choline-phosphotransferase","volume":"16","author":"Roberts","year":"2025","journal-title":"Nat Commun"},{"key":"2026052212174345900_vkag018-B3","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0305-0491(86)90102-1","article-title":"Aspects of phospholipid metabolism in crustaceans as related to changes in environmental temperatures and salinities","volume":"84","author":"Chapelle","year":"1986","journal-title":"Comp Biochem Physiol B"},{"key":"2026052212174345900_vkag018-B4","doi-asserted-by":"crossref","first-page":"6115","DOI":"10.1007\/s10499-024-01458-8","article-title":"Dietary phosphatidylcholine requirements of red swamp crayfish (Procambarus clarkii)","volume":"32","author":"Tian","year":"2024","journal-title":"Aquacult Int"},{"key":"2026052212174345900_vkag018-B5","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1172\/JCI83005","article-title":"Metabolic regulation of immune responses: therapeutic opportunities","volume":"126","author":"Assmann","year":"2016","journal-title":"J Clin Invest"},{"key":"2026052212174345900_vkag018-B6","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.cell.2024.01.030","article-title":"Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis","volume":"187","author":"Qiu","year":"2024","journal-title":"Cell"},{"key":"2026052212174345900_vkag018-B7","doi-asserted-by":"crossref","first-page":"16362","DOI":"10.1021\/jacs.5c02184","article-title":"Self-adaptive release of stem cell-derived exosomes from a multifunctional hydrogel for accelerating MRSA-infected diabetic wound repair","volume":"147","author":"Wang","year":"2025","journal-title":"J Am Chem Soc"},{"key":"2026052212174345900_vkag018-B8","doi-asserted-by":"crossref","first-page":"109689","DOI":"10.1016\/j.fsi.2024.109689","article-title":"Function of hemocyanin-mediated succinate dehydrogenase in glucose metabolism and immunity of Penaeus vannamei","volume":"151","author":"Huang","year":"2024","journal-title":"Fish Shellfish Immunol"},{"key":"2026052212174345900_vkag018-B9","doi-asserted-by":"crossref","first-page":"16771","DOI":"10.1038\/s41598-024-67715-1","article-title":"Shrimp hemocyanin elicits a potent humoral response in mammals and is favorable to hapten conjugation","volume":"14","author":"Sun","year":"2024","journal-title":"Sci Rep"},{"key":"2026052212174345900_vkag018-B10","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.foodchem.2013.02.072","article-title":"Hemocyanin-derived phenoloxidase activity: a contributing factor to hyperpigmentation in Nephrops norvegicus","volume":"140","author":"Coates","year":"2013","journal-title":"Food Chem"},{"key":"2026052212174345900_vkag018-B11","doi-asserted-by":"crossref","first-page":"25889","DOI":"10.1074\/jbc.273.40.25889","article-title":"Tarantula hemocyanin shows phenoloxidase activity","volume":"273","author":"Decker","year":"1998","journal-title":"J Biol Chem"},{"key":"2026052212174345900_vkag018-B12","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.antiviral.2003.08.019","article-title":"Antiviral properties of hemocyanin isolated from shrimp Penaeus monodon","volume":"61","author":"Zhang","year":"2004","journal-title":"Antiviral Res"},{"key":"2026052212174345900_vkag018-B13","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.fsi.2010.11.004","article-title":"Identification and agglutination properties of hemocyanin from the mud crab (Scylla serrata)","volume":"30","author":"Yan","year":"2011","journal-title":"Fish Shellfish Immunol"},{"key":"2026052212174345900_vkag018-B14","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.fsi.2009.05.017","article-title":"Hemocyanin from shrimp Litopenaeus vannamei shows hemolytic activity","volume":"27","author":"Zhang","year":"2009","journal-title":"Fish Shellfish Immunol"},{"key":"2026052212174345900_vkag018-B15","doi-asserted-by":"crossref","first-page":"106566","DOI":"10.1016\/j.intimp.2020.106566","article-title":"Intensive therapy with gastropodan hemocyanins increases their antitumor properties in murine model of colon carcinoma","volume":"84","author":"Stoyanova","year":"2020","journal-title":"Int Immunopharmacol"},{"key":"2026052212174345900_vkag018-B16","doi-asserted-by":"crossref","first-page":"611","DOI":"10.3389\/fimmu.2017.00611","article-title":"C-terminal domain of hemocyanin, a major antimicrobial protein from Litopenaeus vannamei: structural homology with immunoglobulins and molecular diversity","volume":"8","author":"Zhang","year":"2017","journal-title":"Front Immunol"},{"key":"2026052212174345900_vkag018-B17","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1111\/raq.12551","article-title":"The expanding repertoire of immune-related molecules with antimicrobial activity in penaeid shrimps: a review","volume":"13","author":"Aweya","year":"2021","journal-title":"Rev Aquacult"},{"key":"2026052212174345900_vkag018-B18","doi-asserted-by":"crossref","first-page":"158757","DOI":"10.1016\/j.bbalip.2020.158757","article-title":"The sterol regulatory element binding protein homolog of Penaeus vannamei modulates fatty acid metabolism and immune response","volume":"1865","author":"Aweya","year":"2020","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"2026052212174345900_vkag018-B19","doi-asserted-by":"crossref","first-page":"735926","DOI":"10.1016\/j.aquaculture.2020.735926","article-title":"PvHS9 is a novel in silico predicted antimicrobial peptide derived from hemocyanin of Penaeus vannamei","volume":"530","author":"Yang","year":"2021","journal-title":"Aquaculture"},{"key":"2026052212174345900_vkag018-B20","doi-asserted-by":"crossref","first-page":"11494","DOI":"10.3390\/ijms241411494","article-title":"Exploring the antimicrobial potential and biofilm inhibitory properties of hemocyanin from Hemifusus pugilinus (Born, 1778)","volume":"24","author":"Jeyachandran","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026052212174345900_vkag018-B21","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.4049\/jimmunol.2100746","article-title":"The microbial composition of penaeid shrimps\u2019 hepatopancreas is modulated by hemocyanin","volume":"207","author":"Zheng","year":"2021","journal-title":"J Immunol"},{"key":"2026052212174345900_vkag018-B22","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3354\/dao02919","article-title":"Acute hepatopancreatic necrosis disease (AHPND) outbreaks in Penaeus vannamei and P. monodon cultured in the Philippines","volume":"116","author":"de la Pe\u00f1a","year":"2015","journal-title":"Dis Aquat Organ"},{"key":"2026052212174345900_vkag018-B23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s10499-019-00451-w","article-title":"Diagnosis and potential treatments for acute hepatopancreatic necrosis disease (AHPND): a review","volume":"28","author":"Santos","year":"2020","journal-title":"Aquac Int"},{"key":"2026052212174345900_vkag018-B24","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1128\/AEM.03610-14","article-title":"Field and experimental evidence of Vibrio parahaemolyticus as the causative agent of acute hepatopancreatic necrosis disease of cultured shrimp (Litopenaeus vannamei) in northwestern Mexico","volume":"81","author":"Soto-Rodriguez","year":"2015","journal-title":"Appl Environ Microbiol"},{"key":"2026052212174345900_vkag018-B25","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.fsi.2015.06.032","article-title":"Oxidative stress response of the black tiger shrimp Penaeus monodon to Vibrio parahaemolyticus challenge","volume":"46","author":"Duan","year":"2015","journal-title":"Fish Shellfish Immunol"},{"key":"2026052212174345900_vkag018-B26","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.fsi.2009.08.001","article-title":"Immune response and gene expression in shrimp (Litopenaeus vannamei) hemocytes and hepatopancreas against some pathogen-associated molecular patterns","volume":"27","author":"Ji","year":"2009","journal-title":"Fish Shellfish Immunol"},{"key":"2026052212174345900_vkag018-B27","doi-asserted-by":"crossref","first-page":"103958","DOI":"10.1016\/j.isci.2022.103958","article-title":"The ARM repeat domain of hemocyanin interacts with MKK4 to modulate antimicrobial peptides expression","volume":"25","author":"Aweya","year":"2022","journal-title":"iScience"},{"key":"2026052212174345900_vkag018-B28","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1037\/a0028087","article-title":"Testing the significance of a correlation with nonnormal data: comparison of Pearson, Spearman, transformation, and resampling approaches","volume":"17","author":"Bishara","year":"2012","journal-title":"Psychol Methods"},{"key":"2026052212174345900_vkag018-B29","doi-asserted-by":"crossref","first-page":"108175","DOI":"10.1016\/j.intimp.2021.108175","article-title":"Regulation of Sirt1 on energy metabolism and immune response in rheumatoid arthritis","volume":"101","author":"Wu","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"2026052212174345900_vkag018-B30","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/j.bbamem.2017.04.006","article-title":"The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease","volume":"1859","author":"van der Veen","year":"2017","journal-title":"Biochim Biophys Acta Biomembr"},{"key":"2026052212174345900_vkag018-B31","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12860-014-0043-3","article-title":"Two different pathways of phosphatidylcholine synthesis, the Kennedy pathway and the lands cycle, differentially regulate cellular triacylglycerol storage","volume":"15","author":"Moessinger","year":"2014","journal-title":"BMC Cell Biol"},{"key":"2026052212174345900_vkag018-B32","doi-asserted-by":"crossref","first-page":"2546066","DOI":"10.1080\/21505594.2025.2546066","article-title":"Hemocyanin controls Vibrio levels in hemolymph by modulating intracellular ROS via p38 MAPK","volume":"16","author":"Cheng","year":"2025","journal-title":"Virulence"},{"key":"2026052212174345900_vkag018-B33","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.cbpa.2013.04.003","article-title":"Role of redox metabolism for adaptation of aquatic animals to drastic changes in oxygen availability","volume":"165","author":"Welker","year":"2013","journal-title":"Comp Biochem Physiol A Mol Integr Physiol"},{"key":"2026052212174345900_vkag018-B34","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41577-020-00478-8","article-title":"Redox regulation of immunometabolism","volume":"21","author":"Muri","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"2026052212174345900_vkag018-B35","doi-asserted-by":"crossref","first-page":"740953","DOI":"10.1016\/j.aquaculture.2024.740953","article-title":"Nox-derived ROS modulates the antibacterial immune responses in coelomocytes of Apostichopus japonicus","volume":"588","author":"Yang","year":"2024","journal-title":"Aquaculture"},{"key":"2026052212174345900_vkag018-B36","doi-asserted-by":"crossref","first-page":"10520","DOI":"10.3390\/ijms231810520","article-title":"Shrimp lipid droplet protein perilipin involves in the pathogenesis of AHPND-causing Vibrio parahaemolyticus","volume":"23","author":"Wang","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026052212174345900_vkag018-B37","doi-asserted-by":"crossref","first-page":"238","DOI":"10.5551\/jat1994.7.238","article-title":"Lysophosphatidylcholine enhances superoxide anions production via endothelial NADH\/NADPH oxidase","volume":"7","author":"Takeshita","year":"2000","journal-title":"J Atheroscler Thromb"},{"key":"2026052212174345900_vkag018-B38","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1016\/j.cmet.2024.07.024","article-title":"Mitochondrial membrane lipids in the regulation of bioenergetic flux","volume":"36","author":"Decker","year":"2024","journal-title":"Cell Metab"},{"key":"2026052212174345900_vkag018-B39","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1111\/j.1471-4159.2009.06231.x","article-title":"Oxidized phosphatidylcholine formation and action in oligodendrocytes","volume":"110","author":"Qin","year":"2009","journal-title":"J Neurochem"},{"key":"2026052212174345900_vkag018-B40","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1172\/JCI97944","article-title":"Phospholipid signaling in innate immune cells","volume":"128","author":"O\u2019Donnell","year":"2018","journal-title":"J Clin Invest"},{"key":"2026052212174345900_vkag018-B41","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s44466-025-00001-5","article-title":"Phospholipid metabolism in innate immunity and inflammation: from basic to clinic","volume":"1","author":"Liu","year":"2025","journal-title":"Immunity Inflamm"},{"key":"2026052212174345900_vkag018-B42","doi-asserted-by":"crossref","first-page":"e46594","DOI":"10.1371\/journal.pone.0046594","article-title":"Reactive oxygen species in unstimulated hemocytes of the Pacific oyster Crassostrea gigas: a mitochondrial involvement","volume":"7","author":"Donaghy","year":"2012","journal-title":"PLoS One"},{"key":"2026052212174345900_vkag018-B43","doi-asserted-by":"crossref","first-page":"106575","DOI":"10.1016\/j.aquatox.2023.106575","article-title":"Duox mediated ROS production inhibited WSSV replication in Eriocheir sinensis under short-term nitrite stress","volume":"260","author":"Jia","year":"2023","journal-title":"Aquat Toxicol"},{"key":"2026052212174345900_vkag018-B44","doi-asserted-by":"crossref","first-page":"628991","DOI":"10.3389\/fcell.2021.628991","article-title":"From flies to men: ROS and the NADPH oxidase in phagocytes","volume":"9","author":"Mansoori Moghadam","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2026052212174345900_vkag018-B45","first-page":"1737","article-title":"Reactive oxygen species as universal constraints in life-history evolution","volume":"276","author":"Dowling","year":"2009","journal-title":"Proc Biol Sci"},{"key":"2026052212174345900_vkag018-B46","doi-asserted-by":"crossref","first-page":"5745","DOI":"10.1002\/ece3.1790","article-title":"Oxidative stress and life histories: unresolved issues and current needs","volume":"5","author":"Speakman","year":"2015","journal-title":"Ecol Evol"},{"key":"2026052212174345900_vkag018-B47","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.apsb.2022.09.006","article-title":"The role of phosphatidylcholine 34:1 in the occurrence, development and treatment of ulcerative colitis","volume":"13","author":"Yu","year":"2023","journal-title":"Acta Pharm Sin B"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/215\/3\/vkag018\/67387255\/vkag018.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/215\/3\/vkag018\/67387255\/vkag018.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T16:17:57Z","timestamp":1779466677000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/doi\/10.1093\/jimmun\/vkag018\/8527214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3,17]]}},"URL":"https:\/\/doi.org\/10.1093\/jimmun\/vkag018","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2026,3]]},"article-number":"vkag018"}}