Serine Metabolism Tunes Immune Responses To Promote Oreochromis niloticus Survival upon Edwardsiella tarda Infection

Overactive immune response is a critical factor triggering host death upon bacterial infection. However, the mechanism behind the regulation of excessive immune responses is still largely unknown, and the corresponding control and preventive measures are also to be explored. In this study, we find that the Nile tilapia, Oreochromis niloticus, died from Edwardsiella tarda infection had higher level of immune responses than those survived. Such immune responses are strongly associated with the metabolism that was altered at 6 h post-infection. By GC-MS-based metabolome profiling, we identify glycine, serine and threonine metabolism as the top three of the most impacted pathways, which were not properly activated in the fish died out of infection. Serine is one of the crucial biomarkers. Exogenous serine can promote O. niloticus survival both as prophylactic and therapeutic upon E. tarda infection. Our further analysis revealed that exogenous serine flux into the glycine, serine and threonine metabolism, and more importantly, to the glutathione metabolism via glycine. The increased glutathione synthesis could downregulate reactive oxygen species. Therefore, these data together suggest that metabolic modulation of immune responses could be a potential preventive strategy to control overactive immune responses.