Metabolic Mechanism for L-Leucine-Induced Metabolome To Eliminate Streptococcus iniae
Metabolic Mechanism for L-Leucine-Induced Metabolome To Eliminate Streptococcus iniae
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(L)-亮氨酸诱导的代谢组消除海豚链球菌的代谢机制
DOI：
10.1021/acs.jproteome.6b00944
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发表时间：
2017-05-01
影响因子：
4.4
通讯作者：
Peng, Xuan-xian
中科院分区：
文献类型：
--
作者：
Du, Chao-chao;Yang, Man-jun;Peng, Xuan-xian
已有文献记载，关键代谢物可调节宿主代谢组以清除细菌病原体，但代谢机制在很大程度上仍不明确。本研究探索了（L）-亮氨酸诱导的代谢组清除罗非鱼海豚链球菌的代谢机制。基于气相色谱 - 质谱联用（GC - MS）的代谢组学方法被用于研究外源性L - 亮氨酸存在下罗非鱼肝脏的代谢谱。确定了37种丰度有差异的代谢物，并富集了11条代谢途径。模式识别分析确定丝氨酸和脯氨酸为关键代谢物，这两种代谢物在海豚链球菌感染后存活的罗非鱼中被鉴定出来，表明这两种代谢物在L - 亮氨酸诱导宿主清除病原体过程中发挥关键作用。外源性L - 丝氨酸降低了感染海豚链球菌的罗非鱼的死亡率，为这一结论提供了有力证据。此外，外源性L - 丝氨酸提高了罗非鱼脾脏中白细胞介素 - 1β（IL - 1β）和白细胞介素 - 8（IL - 8）基因的表达，但对肿瘤坏死因子α（TNFα）、CXC趋化因子受体4（CXCR4）和Mx基因的表达无影响，这表明该代谢物促进了巨噬细胞的吞噬作用，这与L - 亮氨酸促进巨噬细胞杀灭革兰氏阳性和革兰氏阴性细菌病原体的发现相一致。因此，外源性L - 亮氨酸增强吞噬能力部分归因于L - 丝氨酸的升高。这些结果揭示了外源性L - 亮氨酸调节罗非鱼代谢组以增强先天免疫和清除病原体的一种代谢机制。
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.