Innate antimicrobial peptide protects the skin from invasive bacterial infection
Innate antimicrobial peptide protects the skin from invasive bacterial infection
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DOI：
10.1038/35106587
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发表时间：
2001-11-22
期刊：
影响因子：
64.8
通讯作者：
Gallo, RL
中科院分区：
文献类型：
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作者：
Nizet, V;Ohtake, T;Gallo, RL
在哺乳动物中，几个基因家族编码具有抗菌活性的肽，例如β-防御素和凯萨林菌素（1-3）。这些肽在上皮表面和中性粒细胞中表达，并且已经被提出通过充当“天然抗感染剂”来提供抵抗感染的第一道防线（4，5）。抗微生物肽的保护作用受到质疑，因为观察到这些肽中的几种容易失活（6-8）并且具有不同于体外证明的抗微生物活性的多种细胞作用（9-13）。为了研究特定抗菌肽在皮肤感染小鼠模型中的功能，我们将哺乳动物和细菌遗传学方法结合应用于凯萨林菌素抗菌基因家族（14）。成熟的人（LL-37）（15）和小鼠（CRAMP）（16）肽由相似的基因（分别为CAMP和Cnlp）编码，并且具有相似的α螺旋结构、抗微生物活性谱和组织分布。在这里，我们表明，cathelicidins是一个重要的天然组成部分的先天性宿主防御在小鼠中，并提供保护，防止坏死的皮肤感染所造成的A组链球菌（GAS）。
In mammals, several gene families encode peptides with antibacterial activity, such as the beta -defensins and cathelicidins(1-3). These peptides are expressed on epithelial surfaces and in neutrophils, and have been proposed to provide a first line of defence against infection by acting as 'natural antibiotics'(4,5). The protective effect of antimicrobial peptides is brought into question by observations that several of these peptides are easily inactivated(6-8) and have diverse cellular effects that are distinct from antimicrobial activity demonstrated in vitro(9-13). To investigate the function of a specific antimicrobial peptide in a mouse model of cutaneous infection, we applied a combined mammalian and bacterial genetic approach to the cathelicidin antimicrobial gene family(14). The mature human (LL-37)(15) and mouse (CRAMP)(16) peptides are encoded by similar genes (CAMP and Cnlp, respectively), and have similar alpha -helical structures, spectra of antimicrobial activity and tissue distribution. Here we show that cathelicidins are an important native component of innate host defence in mice and provide protection against necrotic skin infection caused by Group A Streptococcus (GAS).