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

ABSTRACT: 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.

INSTRUMENT(S): Gas Chromatography MS -

SUBMITTER: daixiao yangdx3@mail2.sysu.edu.cn

PROVIDER: MTBLS2974 | MetaboLights | 2021-08-18

REPOSITORIES: MetaboLights

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Project description:Background: While the mechanisms underlying the lactation-induced adaptations of intermediary metabolism and immune response have been extensively studied in rodents and dairy cows, little is known in this regard in sows. Therefore, the present study aimed to explore the lactation-induced changes in hepatic gene expression in sows during lactation. Results: Using a porcine whole-genome microarray a total of 632 differentially expressed genes in the liver of lactating compared to non-lactating sows (each n = 10) could be identified. Enrichment analysis revealed that the differentially expressed genes were mainly involved in fatty acid metabolism, pyruvate metabolism, glutathione metabolism, glycine, serine and threonine metabolism, citrate cycle, glycerophospholipid metabolism, PPAR signaling, nitrogen metabolism, and focal adhesion. The most striking observation with respect to intermediary metabolism was that genes involved in fatty acid catabolism, the catabolism of gluconeogenic amino acids, the citrate cycle and the respiratory chain were up-regulated in the liver of sows during lactation. With respect to immune response, it could be demonstrated that genes encoding acute phase proteins and genes involved in tissue repair were up-regulated and genes encoding focal adhesion molecules were down-regulated in the liver of sows during lactation. Conclusion: The results from this study indicate that energy-generating pathways and pathways involved in the delivery of gluconeogenic substrates are induced in the liver of sows during lactation. The alterations of expression of genes encoding proteins involved in immune response suggest that lactation in sows may cause an adaptive immune response which possibly counteracts hepatic inflammation. For microarray analyses, four RNA pools each, for the non-lactating group (n = 4) and the lactating group (n = 4), were prepared from eight individual sows per group. To each RNA pool, RNA from two different sows per group contributed identical amounts of RNA.

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

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