Hypusination Orchestrates the Antimicrobial Response of Macrophages.
Hypusination Orchestrates the Antimicrobial Response of Macrophages.
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DOI：
10.1016/j.celrep.2020.108510
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发表时间：
2020-12-15
期刊：
影响因子：
8.8
通讯作者：
Wilson KT
中科院分区：
文献类型：
--
作者：
Gobert AP;Finley JL;Latour YL;Asim M;Smith TM;Verriere TG;Barry DP;Allaman MM;Delagado AG;Rose KL;Calcutt MW;Schey KL;Sierra JC;Piazuelo MB;Mirmira RG;Wilson KT
骨髓细胞的先天反应通过诱导效应子防御病原菌。脱氧羟腐胺赖氨酸合酶（DHPS）催化亚精胺的N-部分转移到真核生物翻译起始因子5A（EIF 5A）的赖氨酸-50残基以形成氨基酸羟腐胺赖氨酸。Hypusinated EIF 5A（EIF 5AHyp）将特定的mRNA转运到核糖体进行翻译。我们发现，DHPS是由两种胃肠道病原体，幽门螺杆菌和啮齿类柠檬酸杆菌诱导的巨噬细胞，导致EIF 5A的hypusination增强。在H.幽门胃炎此外，我们确定了细菌诱导的免疫效应调节羟腐胺赖氨酸。这组蛋白质包括抗菌反应和自噬的基本成分。骨髓细胞特异性缺失Dhps的小鼠在巨噬细胞中表现出减少的EIF 5AHyp和增加的细菌负荷和炎症。因此，通过羟腐胺赖氨酸化调节翻译是真核宿主防御病原菌的关键标志。Gobert等人证明，细菌在巨噬细胞中诱导羟腐胺赖氨酸化（hypusination），这是一种调节翻译的特定机制。诱导型抗菌效应物的翻译需要Hypusination。在巨噬细胞中特别缺乏羟腐胺赖氨酸化的小鼠对幽门螺杆菌和啮齿类柠檬酸杆菌（胃肠道的两种病原体）高度易感。
Innate responses of myeloid cells defend against pathogenic bacteria via inducible effectors. Deoxyhypusine synthase (DHPS) catalyzes the transfer of the N-moiety of spermidine to the lysine-50 residue of eukaryotic translation initiation factor 5A (EIF5A) to form the amino acid hypusine. Hypusinated EIF5A (EIF5AHyp) transports specific mRNAs to ribosomes for translation. We show that DHPS is induced in macrophages by two gastrointestinal pathogens, Helicobacter pylori and Citrobacter rodentium, resulting in enhanced hypusination of EIF5A. EIF5AHyp was also increased in gastric macrophages from patients with H. pylori gastritis. Furthermore, we identify the bacteria-induced immune effectors regulated by hypusination. This set of proteins includes essential constituents of antimicrobial response and autophagy. Mice with myeloid cell-specific deletion of Dhps exhibit reduced EIF5AHyp in macrophages and increased bacterial burden and inflammation. Thus, regulation of translation through hypusination is a critical hallmark of the defense of eukaryotic hosts against pathogenic bacteria. Gobert et al. demonstrate that hypusination, a specific mechanism regulating translation, is induced in macrophages by bacteria. Hypusination is required for the translation of inducible antimicrobial effectors. Mice that specifically lack hypusination in macrophages are highly susceptible to Helicobacter pylori and Citrobacter rodentium, two pathogens of the gastrointestinal tract.
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