Development of immunity-based strategy to manage bacterial infection is urgently needed in aquaculture due to the widespread of antibiotic-resistant bacteria. Phagocytosis serves as the first line defense in innate immunity that engulfs bacteria and restricts their proliferations and invasions. However, the mechanism underlying the regulation of phagocytosis is not fully elucidated and the way to boost phagocytosis is not yet explored. In this manuscript, we profiled the metabolomes of monocytes/macrophages isolated from Nile tilapia, prior and after phagocytosis on Vibrio alginolyticus. Monocytes/macrophages showed a metabolic shift following phagocytosis. Interestingly, succinate was accumulated after phagocytosis and was identified as a crucial biomarker to distinguish before and after phagocytosis. Exogenous succinate increased the phagocytotic rate of monocytes/macrophages in a dose-dependent manner. This effect was dependent on the TCA cycle as the inhibitor of malonate that targets succinate dehydrogenase abrogated the effect. Meanwhile, exogenous succinate regulated the expression of genes associated with innate immune and phagocytosis. In addition, succinate-potentiated phagocytosis was applicable to both gram-negative and -positive cells, including V. alginolyticus, Edwardsiella tarda, Streptococcus agalactiae, and Streptococcus iniae. Our study shed light on the understanding of how modulation on host’s metabolism regulates immune response, and this can be a potent therapeutic approach to control bacterial infections in aquaculture.

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Aquatic food is becoming an important food source that provides micronutrients to human beings. The decline of wild aquatic animals makes aquaculture become increasingly important to play this role. However, infectious diseases, especially bacterial infection, represent severe threat to aquaculture, which causes huge economic loss. Meanwhile, strategies in managing bacterial infection in an antibiotic-independent way are still lacking. In this study, we monitor the metabolomic shift of crucian carp upon Aeromonas hydrophila infection. We find that the metabolism of the fish that died of infection is distinct from the ones that survived. By multivariate analysis, we identify fructose as a crucial biomarker whose abundance is significantly different from the dying and surviving groups where the surviving group has a higher content of fructose than the dying group. Exogenous supplementation of fructose increases fish survival rate by 27.2%. Quantitative gene expression analysis demonstrated that fructose enhances the expression of lysozyme and complement 3 expression, which is also confirmed in the serum level. Furthermore, the augmented lysozyme and C3 levels enhance serum cell lytic activity which contribute to the reduced bacterial load in vivo. Thus, our study demonstrates a metabolism-based approach to manage bacterial infection through modulating immune response to clear bacterial infection.