The Keap1-Nrf2 signaling pathway regulates antioxidant defenses of Ctenopharyngodon idella induced by bacterial infection

Respiratory burst is a process involving rapid production of reactive oxygen species (ROS) for eliminating invading pathogens. However, excessive ROS production can be fatal to the host organism. The Keap1-Nrf2-ARE (Kelch-like ECH-associated protein 1 [Keap1]; Nuclear factor erythroid-derived 2-like 2 [Nrf2]; Antioxidant responsive element [ARE]) signaling pathway plays an important role in alleviating oxidative stress and preserving cellular homeostasis. However, the role of Keap1 during bacterial infection in fish remains unclear. In this study, we cloned and characterized the Keap1 gene of grass carp (CiKeap1) for the first time. CiKeap1 encodes a 593-amino acid protein of the Keap1b type. The tissue distribution analysis data revealed that the brain contains the highest transcription level of Keap1, followed by the heart and liver. The infection of Aeromonas hydrophila and Staphylococcus aureus obviously modulated the gene transcription and protein expression levels of Keap1, which suggested that the CiKeap1 participates in antibacterial immune responses. Furthermore, in vitro overexpression assays clarified the defensive and regular roles of CiKeap1 in maintaining host redox homeostasis in response to bacterial infection through the Keap1-Nrf2-ARE signaling pathway. In conclusion, the present results provide an expanded perspective on the role of Keap1 in teleost immunology that can guide healthy farming cultivation of grass carp.