TAK1 confers antibacterial protection through mediating the activation of MAPK and NF-κB pathways in shrimp

Abstract

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 knockdown in vivo also inhibited the nuclear translocation of c-Jun and Relish during V. parahaemolyticus infection. Accordingly, ectopic expression of shrimp TAK1 in Drosophila S2 cells increased the cleavage of co-expressed shrimp Relish, and induced the promoter activity of Relish targeted gene Diptericin (Dpt). Furthermore, knockdown of c-Jun and Relish enhanced the sensitivity of shrimp to V. parahaemolyticus infection. 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.