CLIC2α Chloride Channel Orchestrates Immunomodulation of Hemocyte Phagocytosis and Bactericidal Activity in Crassostrea gigas
Xiangyu Zhang,
Fan Mao,
Nai-Kei Wong,
Yongbo Bao,
Yue Lin,
Kunna Liu,
Jun Li,
Zhiming Xiang,
Haitao Ma,
Shu Xiao,
Yang Zhang,
Ziniu Yu
Affiliations
Xiangyu Zhang
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, Innovation Academy of South China Sea Ecology and Environmental Engineering (ISEE), South China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou 510301, P. R. China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 510301, P. R. China; University of Chinese Academy of Sciences, Beijing 100049, P. R. China
Fan Mao
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, Innovation Academy of South China Sea Ecology and Environmental Engineering (ISEE), South China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou 510301, P. R. China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 510301, P. R. China
Nai-Kei Wong
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, Innovation Academy of South China Sea Ecology and Environmental Engineering (ISEE), South China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou 510301, P. R. China; National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, P. R. China
Yongbo Bao
Zhejiang Key Laboratory of Aquatic Germplasm Resources, College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, P. R. China
Yue Lin
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, Innovation Academy of South China Sea Ecology and Environmental Engineering (ISEE), South China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou 510301, P. R. China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 510301, P. R. China; University of Chinese Academy of Sciences, Beijing 100049, P. R. China
Kunna Liu
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, Innovation Academy of South China Sea Ecology and Environmental Engineering (ISEE), South China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou 510301, P. R. China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 510301, P. R. China; University of Chinese Academy of Sciences, Beijing 100049, P. R. China
Jun Li
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, Innovation Academy of South China Sea Ecology and Environmental Engineering (ISEE), South China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou 510301, P. R. China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 510301, P. R. China
Zhiming Xiang
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, Innovation Academy of South China Sea Ecology and Environmental Engineering (ISEE), South China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou 510301, P. R. China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 510301, P. R. China
Haitao Ma
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, Innovation Academy of South China Sea Ecology and Environmental Engineering (ISEE), South China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou 510301, P. R. China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 510301, P. R. China
Shu Xiao
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, Innovation Academy of South China Sea Ecology and Environmental Engineering (ISEE), South China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou 510301, P. R. China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 510301, P. R. China
Yang Zhang
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, Innovation Academy of South China Sea Ecology and Environmental Engineering (ISEE), South China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou 510301, P. R. China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 510301, P. R. China; Corresponding author
Ziniu Yu
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, Innovation Academy of South China Sea Ecology and Environmental Engineering (ISEE), South China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou 510301, P. R. China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 510301, P. R. China; Corresponding author
Summary: 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− channel gene responsible for regulating Cl− influx in oysters. Knockdown of CLIC2α predictably impeded phagosome acidification and restricted bacterial killing in oysters. In conclusion, our work has established CLIC2α as a prominent regulator of Cl− influx and thus Cl− function in C. gigas in bacterial infection contexts.
