TAK1 confers antibacterial protection through mediating the activation of MAPK and NF-κB pathways in shrimp.
TAK1 confers antibacterial protection through mediating the activation of MAPK and NF-κB pathways in shrimp.
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DOI：
10.1016/j.fsi.2022.03.008
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发表时间：
2022-03
影响因子：
4.7
通讯作者：
Sheng Wang;Haoyang Li;Rongjian Chen;Xiewu Jiang;Jianguo He;Chaozheng Li
中科院分区：
文献类型：
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作者：
Sheng Wang;Haoyang Li;Rongjian Chen;Xiewu Jiang;Jianguo He;Chaozheng Li
MAPK和NF-κ B通路是多细胞动物天然免疫系统的重要组成部分。在一些模式生物中，已显示MAP 3-激酶TGF-β激活的激酶1（TAK1）调节MAPK和NF-κ B途径活化以定制对病原体或感染的免疫应答。然而，这一过程在虾中并不完全清楚。本研究以副溶血性弧菌（Vibrio parahaemolyticus）感染的凡纳滨对虾（Litopenaeus vannamei）为研究对象，研究了TAK 1对凡纳滨对虾MAPK和NF-κ B激活的影响。我们发现，虾TAK1可以激活MAPK和NF-κ B通路的转录因子c-Jun和Relish。具体地说，过表达虾TAK1能够强烈诱导AP-1和NF-κ B报告基因的活性。TAK1被证明可以结合几种MAPK 2激酶，包括MKK 4、MKK 6和MKK 7，并诱导它们的磷酸化，这是MAPK途径激活的标志。TAK1基因敲低也能抑制c-Jun和Relish在V.副溶血感染因此，在果蝇S2细胞中异位表达虾TAK1增加了共表达虾Relish的切割，并诱导了Relish靶基因Diptericin（Dpt）的启动子活性。c-Jun和Relish基因的敲除增强了对虾对病毒的敏感性。副溶血感染这些结果表明，TAK1通过调节MAPK和NF-κ B通路的激活发挥抗菌保护作用，提示TAK1-MAPK/NF-κ B轴可能成为增强甲壳动物抗菌反应的潜在治疗靶点。
MAPK and NF-κB pathways are important components of innate immune system in multicellular animals. In some model organisms, the MAP3-kinase TGF-beta-activated kinase 1 (TAK1) have been shown to regulate both MAPK and NF-κB pathways activation to tailor immune responses to pathogens or infections. However, this process is not fully understood in shrimp. In this study, we investigated the effect of TAK1 on MAPK and NF-κB activation in shrimp Litopenaeus vannamei following Vibrio parahaemolyticus infection. We found that shrimp TAK1 could activate c-Jun and Relish, the transcription factors of MAPK pathway and NF-κB pathway, respectively. Specifically, over-expression of shrimp TAK1 was able to strongly induce the activities of both AP-1 and NF-κB reporters. TAK1 was shown to bind several MAP2-kinases, including MKK4, MKK6 and MKK7, and induced their phosphorylations, the hallmarks for MAPK pathways activation. TAK1 knockdownin vivoalso inhibited the nuclear translocation of c-Jun and Relish duringV. parahaemolyticusinfection. Accordingly, ectopic expression of shrimp TAK1 inDrosophilaS2 cells increased the cleavage of co-expressed shrimp Relish, and induced the promoter activity of Relish targeted geneDiptericin(Dpt). Furthermore, knockdown of c-Jun and Relish enhanced the sensitivity of shrimp toV. parahaemolyticusinfection. These findings indicated that shrimp TAK1 conferred antibacterial protection through regulating the activation of both MAPK pathway and NF-κB pathway, and suggested that the TAK1-MAPK/NF-κB axis could be a potential therapeutic target for enhancing antibacterial responses in crustaceans.