State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, PR China; Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, Sun Yat-sen University, Guangzhou, PR China.
School of Marine Biology and Fisheries, Hainan University, Haikou, China.
Fish Shellfish Immunol. 2023 Nov;142:109123. doi: 10.1016/j.fsi.2023.109123. Epub 2023 Oct 7.
The NF-κB pathway plays an important role in immune regulation. Basigin, an immunoglobulin superfamily membrane protein, is involved in the activation of NF-κB. However, its role in NF-κB signaling in response to pathogen infection remains unclear. In this study, we identified the Basigin gene from Pacific white shrimp, Penaeus vannamei, a representative species for studying the innate immune system of invertebrates. Basigin promoted the degradation of the IκB homolog Cactus, facilitated the nuclear translocation of the NF-κB family member Dorsal, and positively regulated the expression of Dorsal pathway downstream antimicrobial peptide genes. Interestingly, recombinant Basigin protein could bind a variety of Gram-positive and Gram-negative bacteria. Silencing of Basigin inhibited the Dorsal signaling activated by V. parahaemolyticus infection and significantly decreased the survival rate of V. parahaemolyticus-infected shrimp. The expression levels of the antimicrobial peptides ALF1 and ALF2 were downregulated, and the phagocytosis of hemocytes was attenuated in Basigin-silenced shrimp. Similar results were observed in shrimp treated with a recombinant extracellular region of the Basigin protein that was able to compete with endogenous Basigin. Therefore, to the best of our knowledge, this study is the first to demonstrate the function of Basigin as a pathogen recognition receptor that activates NF-κB signaling for antibacterial immunity in shrimp.
NF-κB 通路在免疫调节中发挥重要作用。Basigin 是免疫球蛋白超家族的膜蛋白，参与 NF-κB 的激活。然而，其在病原体感染时 NF-κB 信号转导中的作用尚不清楚。本研究从凡纳滨对虾（Penaeus vannamei）中鉴定出 Basigin 基因，该虾是研究无脊椎动物先天免疫系统的代表性物种。Basigin 促进 IκB 同源物 Cactus 的降解，促进 NF-κB 家族成员 Dorsal 的核易位，并正向调节 Dorsal 通路下游抗菌肽基因的表达。有趣的是，重组 Basigin 蛋白可与多种革兰氏阳性和革兰氏阴性细菌结合。Basigin 沉默抑制了副溶血弧菌感染激活的 Dorsal 信号，显著降低了副溶血弧菌感染虾的存活率。抗菌肽 ALF1 和 ALF2 的表达水平下调，且血细胞的吞噬作用减弱。在用能够与内源性 Basigin 竞争的 Basigin 重组细胞外区域处理的虾中观察到类似的结果。因此，据我们所知，本研究首次证明了 Basigin 作为一种病原体识别受体的功能，它可激活 NF-κB 信号通路，从而在虾中发挥抗菌免疫作用。
