{"title":"Exosome-mediated ACSL4 mRNA delivery suppresses WSSV infection by promoting ferroptosis in mud crab","authors":"Xinshan Zhao , Mingming Sun , Yi Gong","doi":"10.1016/j.aquaculture.2024.742078","DOIUrl":null,"url":null,"abstract":"<div><div>As a novel immunomodulator, exosomes can deliver molecules such as mRNA and proteins between cells, providing resistance against pathogen infections. ACSL4, a lipid metabolizing enzyme, has been extensively studied as a well-established regulator of ferroptosis in the immune defense mechanism of vertebrates. However, the role of exosomes and ACSL4-mediated ferroptosis in the antiviral immune response has not been addressed in invertebrates. This study found that exosomes secreted by WSSV-infected mud crabs (<em>Scylla paramamosain</em>) can inhibit viral replication by activating ferroptosis. In addition, ACSL4 mRNA was found to be more packaged in exosomes secreted by hemocytes during viral infection in mud crabs. Then, the role of exosome-mediated ACSL4 mRNA in antiviral immunomodulation was further explored by RNAi methods. The results showed that WSSV-infected exosomes encapsulated with more <em>Sp</em>ACSL4 mRNA could lead to increased Fe<sup>2+</sup>, reactive oxygen species (ROS), and malondialdehyde (MDA) contents, as well as decreased GPX4 expression, so as to activate ferroptosis and further suppress WSSV replication in mud crabs. This study provides novel insights into the innate defense mechanisms of crustaceans.</div></div>","PeriodicalId":8375,"journal":{"name":"Aquaculture","volume":"598 ","pages":"Article 742078"},"PeriodicalIF":3.9000,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aquaculture","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0044848624015400","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"FISHERIES","Score":null,"Total":0}
引用次数: 0
Abstract
As a novel immunomodulator, exosomes can deliver molecules such as mRNA and proteins between cells, providing resistance against pathogen infections. ACSL4, a lipid metabolizing enzyme, has been extensively studied as a well-established regulator of ferroptosis in the immune defense mechanism of vertebrates. However, the role of exosomes and ACSL4-mediated ferroptosis in the antiviral immune response has not been addressed in invertebrates. This study found that exosomes secreted by WSSV-infected mud crabs (Scylla paramamosain) can inhibit viral replication by activating ferroptosis. In addition, ACSL4 mRNA was found to be more packaged in exosomes secreted by hemocytes during viral infection in mud crabs. Then, the role of exosome-mediated ACSL4 mRNA in antiviral immunomodulation was further explored by RNAi methods. The results showed that WSSV-infected exosomes encapsulated with more SpACSL4 mRNA could lead to increased Fe2+, reactive oxygen species (ROS), and malondialdehyde (MDA) contents, as well as decreased GPX4 expression, so as to activate ferroptosis and further suppress WSSV replication in mud crabs. This study provides novel insights into the innate defense mechanisms of crustaceans.
期刊介绍:
Aquaculture is an international journal for the exploration, improvement and management of all freshwater and marine food resources. It publishes novel and innovative research of world-wide interest on farming of aquatic organisms, which includes finfish, mollusks, crustaceans and aquatic plants for human consumption. Research on ornamentals is not a focus of the Journal. Aquaculture only publishes papers with a clear relevance to improving aquaculture practices or a potential application.