Nrf2 modulates host defense during antibacterial immunity response in grass carp (Ctenopharyngodon idellus)

Excessive production of reactive oxygen species (ROS) usually breaks the body's homeostasis and results in oxidative damage. It has been reported that transcription factor NF-E2-related factor 2 (Nrf2) can regulate redox balance for host defense, which activates diverse cyto-protective genes to maintain intracellular homoeostasis during pathogen invasion. Several studies of the immunologic function of Nrf2 have focused on mammals. However, the immunomodulatory role of Nrf2 in response to bacterial infection in teleost is still unclear. In the present study, we analyzed the Ctenopharyngodon idellus Nrf2 (CiNrf2) sequence, and detected the tissue distribution and expression pattern under bacterium invasion. The results showed that CiNrf2 widely existed in all tested tissues and had the highest expression level in liver, followed by the middle kidney and spleen. The expression of CiNrf2 was significantly up-regulated in both mRNA and protein levels during Staphylococcus aureus and Aeromonas hydrophila infection, which suggested CiNrf2 was involved in the antibacterial immunity response. Meanwhile, the stimulation of bacteria could significantly improve the expression of antioxidant genes such as superoxide dismutase 1 (SOD1), catalase (CAT) and glutathione synthetase (GSS). Furthermore, under in vitro LPS or LTA treatment, overexpression of CiNrf2 could activate the expression of antioxidant genes (SOD1, SOD2, CAT, GPX and GSS), and its knockdown effect could suppress the expression of the above antioxidant genes. Taken together, these results confirm the role of CiNrf2 as an antioxidant regulator for the defense system of host in antibacterial immunity. The present results will shed new light on the function of CiNrf2 in the antibacterial immunity of teleost, and also provide a new perspective for disease prevention and control in the grass carp farming industry.