Enterobactin induces the chemokine, interleukin-8, from intestinal epithelia by chelating intracellular iron.
Enterobactin induces the chemokine, interleukin-8, from intestinal epithelia by chelating intracellular iron.
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DOI：
10.1080/19490976.2020.1841548
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发表时间：
2020-11-09
期刊：
影响因子：
12.2
通讯作者：
Vijay-Kumar M
中科院分区：
文献类型：
--
作者：
Saha P;Yeoh BS;Xiao X;Golonka RM;Abokor AA;Wenceslau CF;Shah YM;Joe B;Vijay-Kumar M
铁是哺乳动物和微生物不可或缺的营养素。细菌合成铁载体以螯合宿主铁，而脂质运载蛋白2（Lcn 2）是防止这种铁盗窃的宿主防御蛋白。肠杆菌素（Ent）是一种儿茶酚型铁载体，对铁具有最强的亲和力。肠上皮细胞（IEC）是邻近的大型微生物种群，并与微生物产品，包括Ent接触。我们进行了这项研究，以探讨是否单一的刺激Ent可以影响IEC功能。使用具有不同Lcn 2基础水平的三种人IEC细胞系（即，HT 29 < DLD-1 < Caco-2/BBe），我们证明了无铁Ent可以在HT 29和DLD-1 IEC中诱导促炎趋化因子白细胞介素8（IL-8）的剂量依赖性分泌，但在Caco-2/BBe中不诱导。ENT诱导的IL-8分泌依赖于不稳定铁池的螯合作用和细胞内Lcn 2的水平。因此，Ent处理的HT 29细胞的IL-8分泌可以通过用铁饱和Ent或通过向细胞中加入外源性Lcn 2来基本上抑制。当与其他微生物产物（即鞭毛蛋白、脂多糖）共刺激时，Ent的IL-8产生可以进一步增强。水溶性微生物铁载体没有诱导IL-8的产生，这意味着IEC是专门响应于脂溶性的Ent. Intriguingly，甲酰肽受体（FPR）拮抗剂（即Boc 2，环孢霉素H）废除Ent-induced IL-8，这意味着这样的IEC响应可能是，部分依赖于FPR。综上所述，这些结果表明IEC将Ent感知为危险信号，其中其识别导致IL-8分泌。
Iron is an indispensable nutrient for both mammals and microbes. Bacteria synthesize siderophores to sequester host iron, whereas lipocalin 2 (Lcn2) is the host defense protein that prevent this iron thievery. Enterobactin (Ent) is a catecholate-type siderophore that has one of the strongest known affinities for iron. Intestinal epithelial cells (IECs) are adjacent to large microbial population and are in contact with microbial products, including Ent. We undertook this study to investigate whether a single stimulus of Ent could affect IEC functions. Using three human IEC cell-lines with differential basal levels of Lcn2 (i.e. HT29 < DLD-1 < Caco-2/BBe), we demonstrated that iron-free Ent could induce a dose-dependent secretion of the pro-inflammatory chemokine, interleukin 8 (IL-8), in HT29 and DLD-1 IECs, but not in Caco-2/BBe. Ent-induced IL-8 secretion was dependent on chelation of the labile iron pool and on the levels of intracellular Lcn2. Accordingly, IL-8 secretion by Ent-treated HT29 cells could be substantially inhibited by either saturating Ent with iron or by adding exogenous Lcn2 to the cells. IL-8 production by Ent could be further potentiated when co-stimulated with other microbial products (i.e. flagellin, lipopolysaccharide). Water-soluble microbial siderophores did not induce IL-8 production, which signifies that IECs are specifically responding to the lipid-soluble Ent. Intriguingly, formyl peptide receptor (FPR) antagonists (i.e. Boc2, cyclosporine H) abrogated Ent-induced IL-8, implicating that such IEC response could be, in part, dependent on FPR. Taken together, these results demonstrate that IECs sense Ent as a danger signal, where its recognition results in IL-8 secretion.
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影响因子：
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