Innate Immune Functions of α-Defensins in the Small Intestine
Innate Immune Functions of α-Defensins in the Small Intestine
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DOI：
10.1159/000354681
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发表时间：
2013-01-01
影响因子：
2.3
通讯作者：
Bevins, Charles L.
中科院分区：
文献类型：
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作者：
Bevins, Charles L.
肠粘膜与复杂、密集的微生物群落接触，包括数百种常驻微生物群和许多从食物和水源进入的瞬时微生物。在小肠中，潘氏细胞（专门的分泌上皮细胞）产生大量的α-防御素和其他几种抗生素肽。人类Paneth细胞产生两种α-防御素：HD 5和HD 6。来自体内模型的数据表明，潘氏细胞α-防御素在肠道中防御食物和水传播的病原体中发挥关键作用。这两种α-防御素保护肠道病原体的机制是非常不同的。HD 5是一种有效的抗菌剂，通过膜破坏杀死目标微生物，而HD 6是新发现的自组装形成纤维和纳米网，包围和缠绕细菌。最近的数据表明，HD 5还有助于塑造定植微生物群的组成。人体研究表明，HD 5和HD 6的表达减少是回肠克罗恩病的基本特征。从机制上讲，潘氏细胞α-防御素表达减少与回肠克罗恩病发病机制之间的联系可能是粘膜抗微生物防御减弱和/或肠道微生物群组成改变的结果。(C)2013 S.Karger AG，巴塞尔
The intestinal mucosa interfaces with a complex, dense community of microorganisms, including hundreds of species of resident microbiota and many transient microbes entering from food- and water-borne sources. In the small intestine, Paneth cells (specialized secretory epithelial cells) produce abundant quantities of alpha-defensins and several other antibiotic peptides. Human Paneth cells make two alpha-defensins: HD5 and HD6. Data from in vivo models indicate that Paneth cell alpha-defensins play a pivotal role in defense from food- and water-borne pathogens in the intestine. The mechanism by which these two a-defensins protect from enteric pathogens is quite distinct. HD5 is a potent antimicrobial that kills target microbes by membrane disruption, whereas HD6 is newly discovered to self-assemble to form fibrils and nanonets that surround and entangle bacteria. Recent data suggest that HD5 also serves to help shape the composition of the colonizing microbiota. Studies in humans suggest that reduced expression of HD5 and HD6 is a fundamental feature of ileal Crohn's disease. Mechanistically, the link between reduced Paneth cell alpha-defensin expression and ileal Crohn's disease pathogenesis may be a result of the weakened mucosal antimicrobial defense and/or alterations in the composition of commensal microbiota. (C) 2013 S.Karger AG, Basel