biostudies-literatureZhang XChinese Academy of SciencesScience and Technology Program of Guangzhou, ChinaProgram of the Pearl River Young Talents of Science and Technology in Guangzhou of ChinaChina Agricultural Research SystemDemonstration Project for Innovative Development of Marine EconomyInstitution of South China Sea Ecology and Environmental EngineeringScience and Technology Planning Project of Guangdong Province, ChinaNational Science Foundation of ChinaKey Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory101328https://www.ebi.ac.uk/biostudies/studies/S-EPMC7363696biostudies-literatureUnknown23(7)Chloride ion plays critical roles in modulating immunological interactions. Herein, we demonstrated that the anion channel CLIC2α mediates Cl^- flux to regulate hemocytes functions in the Pacific oyster (Crassostrea gigas). Specifically, during infection by Vibrio parahemolyticus, chloride influx was activated following onset of phagocytosis. Phosphorylation of Akt was stimulated by Cl^- ions entering host cells, further contributing to signal transduction regulating internalization of bacteria through the PI3K/Akt signaling pathway. Concomitantly, Cl^- entered phagosomes, promoted the acidification and maturation of phagosomes, and contributed to production of HOCl to eradicate engulfed bacteria. Finally, genomic screening reveals CLIC2α as a major Cl<sup>-</iScienceCLIC2α Chloride Channel Orchestrates Immunomodulation of Hemocyte Phagocytosis and Bactericidal Activity in Crassostrea gigas.PMC7363696ISEE2018PY01201804020073ISEE2018PY032017B030314052CARS-4931902404ISEE2018ZD01NBHY-2017-S4201707010177201806010003GML2019ZD0407Liu KLi JBao YZhang YZhang XXiang ZMa HWong NKLin YMao FYu ZXiao SfalseCLIC2α Chloride Channel Orchestrates Immunomodulation of Hemocyte Phagocytosis and Bactericidal Activity in Crassostrea gigas.Chloride ion plays critical roles in modulating immunological interactions. Herein, we demonstrated that the anion channel CLIC2α mediates Cl^- flux to regulate hemocytes functions in the Pacific oyster (Crassostrea gigas). Specifically, during infection by Vibrio parahemolyticus, chloride influx was activated following onset of phagocytosis. Phosphorylation of Akt was stimulated by Cl^- ions entering host cells, further contributing to signal transduction regulating internalization of bacteria through the PI3K/Akt signaling pathway. Concomitantly, Cl^- entered phagosomes, promoted the acidification and maturation of phagosomes, and contributed to production of HOCl to eradicate engulfed bacteria. Finally, genomic screening reveals CLIC2α as a major Cl<sup>-</2020-01-01T00:00:00Z2020 Jul2025-04-04T13:26:04.28Z2025-04-04T13:26:04.28ZS-EPMC73636963267405510.1016/j.isci.2020.101328