期刊
JOURNAL OF PROTEOME RESEARCH
卷 16, 期 5, 页码 1880-1889出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.6b00944
关键词
metabolome; leucine; metabolic mechanism; Streptococcus iniae; tilapia
资金
- NSFC [31572654, 31672656]
- Science and Technology Programs of Guangzhou [201504010025]
- Natural Science Foundation of Guangdong [2015A030308009]
- National Key Research and Development Plan [2016YFD0501307]
Crucial metabolites that modulate hosts' metabolome to eliminate bacterial pathogens have been documented, but the metabolic mechanisms are largely unknown. The present study explores the metabolic mechanism for (L)-leucine-induced metabolome to eliminate Streptococcus iniae in tilapia. GC MS-based metabolomics was used to investigate the tilapia liver metabolic profile in the presence of exogenous L-leucine. Thirty-seven metabolites of differential abundance were determined, and 11 metabolic pathways were enriched. Pattern recognition analysis identified serine and praline as crucial metabolites, which are the two metabolites identified in survived tilapias during S. iniae infection, suggesting that the two metabolites play crucial roles in L-leucine-induced elimination of the pathogen by the host. Exogenous L-serine reduces the mortality of tilapias infected by S. iniae, providing a robust proof supporting the conclusion. Furthermore, exogenous L-serine elevates expression of genes IL-1 beta and IL-8 in tilapia spleen, but not TNF alpha, CXCR4 and Mx, suggesting that the metabolite promotes a phagocytosis role of macrophages, which is consistent with the finding that L-leucine promotes macrophages to kill both Gram-positive and Gramnegative bacterial pathogens. Therefore, the ability of phagocytosis enhanced by exogenous L-leucine is partly attributed to elevation of L-serine. These results demonstrate a metabolic mechanism by which exogenous L-leucine modulates tilapias' metabolome to enhance innate immunity and eliminate pathogens.
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