Molecular and functional characterization of MST2 in grass carp during bacterial infection

• Published in: Fish & shellfish immunology 2021-12, Vol.119, p.19-30
• Main Authors: Li, Yanan, Qiu, Xiaolong, Lu, Zhijie, Zhan, Fanbin, Yang, Minxuan, Sarath Babu, V., Li, Jun, Qin, Zhendong, Lin, Li
• Format: Article
• Language: English
• Subjects: Animal Feed - analysis; Animals; Antioxidant regulator; Antioxidants; Bacterial Infections; Carps - genetics; Ctenopharyngodon idella; Diet; Fish Diseases; Fish Proteins - genetics; Immunity, Innate - genetics; Innate immunity; MST2; NF-E2-Related Factor 2
• ISSN: 1050-4648; 1095-9947
• DOI: 10.1016/j.fsi.2021.09.026

The regulation of host redox homeostasis is critically important in the immune response to pathogens. The “mammalian sterile 20-like” kinase 2 (MST2) has been shown to play a role in apoptosis, cell proliferation, and cancer; however, few studies have examined its ability to modulate redox homeostasis during innate immunity, especially in teleost fish. In this study, we cloned the MST2 gene of Ctenopharyngodon idella (CiMST2) and analyzed its tissue distribution. CiMST2 was present in most of the studied tissues, and it was most highly expressed in brain tissue. Expression patterns analysis revealed that MST2 mRNA and protein were significantly up-regulated under bacterial infection, suggesting that it is involved in the immune response. Bacterial stimulation significantly increased the level of antioxidases. To explore the interplay between CiMST2 and antioxidant regulation, we examined the effects of CiMST2 overexpression and conducted RNA interference assays in vitro. CiMST2 overexpression significantly increased the expression levels of nuclear factor E2-related factor 2 (Nrf2) and other antioxidases and vice versa, revealing that CiMST2 regulated host redox homeostasis via Nrf2-antioxidant responsive element (ARE) signaling. Overall, our findings provide a new perspective on the role of MST2 in innate immunity in teleosts as well as insights that will aid the prevention and control of disease in the grass carp farming industry. 1.Mst2 widely existed in all tested tissues in healthy grass carp.2.The bacterial infection significantly up-regulated the expression of CiMst2.3.The bacterial infection significantly up-regulated the antioxidant system of grass carp.4.CiMst2 plays a vital antioxidant regulator in antibacterial immunity through Nrf2-ARE signaling.