Lipocalin 2 regulates intestine bacterial survival by interplaying with siderophore in a weaned piglet model of Escherichia coli infection.

Lipocalin 2 regulates intestine bacterial survival by interplaying with siderophore in a weaned piglet model of Escherichia coli infection.
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在大肠杆菌感染的断奶仔猪模型中,脂质运载蛋白 2 通过与铁载体相互作用来调节肠道细菌存活

DOI:
10.18632/oncotarget.18528
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发表时间:
2017-09-12
期刊:
影响因子:
--
通讯作者:
Du HH
Du HH
中科院分区:
其他
文献类型:
--
作者:
Guo BX;Wang QQ;Li JH;Gan ZS;Zhang XF;Wang YZ;Du HH

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铁是一种促进细胞增殖和生长的必需营养物质,在调节哺乳动物宿主和病原体之间的生存之战中发挥着关键作用。病原菌分泌铁载体从宿主获取铁。然而,Lipocalin 2(Lcn2)是一种铁载体结合的抗菌蛋白,它与铁载体结合以阻止细菌摄取铁,这对控制全身感染大肠杆菌至关重要。但很少有研究关注Lcn2通过微生物铁代谢抑制细菌增殖在肠道中的抗感染作用。在这项研究中,我们证明了在大肠杆菌K88感染的仔猪模型中,铁被隔离在细胞内。大肠杆菌K88感染后产生铁载体,在体外缺铁环境中铁载体相关基因表达上调。同时,我们发现Lcn2在空肠组织中的表达被大肠杆菌K88感染后迅速而强烈地诱导表达,并且可以被IL-17和IL-22刺激。此外,在上皮细胞IPEC-1中诱导的Lcn2和以重组蛋白形式外源添加的Lcn2均能抑制大肠杆菌的生长。由此可以得出结论:Lcn2是抵抗E.ColiK88肠道感染的粘膜免疫防御的重要组成部分。
Iron is an essential nutrient that facilitates cell proliferation and growth, which plays a pivotal role in modulating the battle for survival between mammalian hosts and their pathogens. Pathogenic bacteria secrete siderophores to acquire iron from the host. However, lipocalin 2 (Lcn2), a siderophore-binding antimicrobial protein, binds to siderophores to prevent bacterial uptake of iron, which is critical for the control of systemic infection with Escherichia coli (E. coli). But few studies focus on the anti-infective response of Lcn2 in the intestines by inhibiting bacterial proliferation based on microbial iron metabolism. In this study, we showed that iron was sequestrated within cells in a piglet model of E. coli K88 infection. Siderophores was produced following E. coli K88 infection and siderophore-related genes expression was upregulated in iron-deficiency environment in vitro. Meanwhile, we found that Lcn2 expression was rapidly and robustly induced in jejunum by E. coli K88 infection and could be stimulated by IL-17 and IL-22. Furthermore, both Lcn2 induced in epithelial cells IPEC-1 and added exogenously as a recombinant protein could inhibit the growth of E. coli. We can conclude that Lcn2 is a crucial component of mucosal immune defense against intestinal infection with E. coli K88.
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