Critical Role of Antimicrobial Peptide Cathelicidin for Controlling Helicobacter pylori Survival and Infection

Critical Role of Antimicrobial Peptide Cathelicidin for Controlling Helicobacter pylori Survival and Infection
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抗菌肽 Cathelicidin 对于控制幽门螺杆菌生存和感染的关键作用

DOI:
10.4049/jimmunol.1500021
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发表时间:
2016-02
影响因子:
4.4
通讯作者:
Cho CH
Cho CH
中科院分区:
医学2区
文献类型:
--
作者:
Zhang L;Wu WKK;Gallo RL;Fang EF;Hu W;Ling TKW;Shen J;Chan RLY;Lu L;Luo XM;Li MX;Chan KM;Yu J;Wong VWS;Ng SC;Wong SH;Chan FKL;Sung JJY;Chan MTV;Cho CH

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抗菌肽抗菌肽对预防不同种类的微生物感染至关重要。本研究旨在阐明抗菌肽对幽门螺杆菌感染及其相关胃炎的保护作用。外源性抗菌肽抑制幽门螺杆菌生长,破坏细菌生物膜,诱导幽门螺杆菌膜形态改变。此外,在人胃上皮HFE-145细胞中敲低内源性cathelicidin可显著提高幽门螺杆菌的细胞内存活率。与此一致的是,在幽门螺杆菌感染后,cathelicidin敲除小鼠的胃粘膜中,幽门螺杆菌定植更强,促炎细胞因子IL-6、IL-1β和ICAM1的表达更高,抗炎细胞因子IL-10的表达更低。在野生型小鼠中,幽门螺杆菌感染也刺激了胃上皮源性抗菌肽的产生。重要的是,活性分泌抗菌肽的生物工程乳酸乳球菌预处理显著增加了粘膜抗菌肽水平,减少了幽门螺杆菌感染和相关炎症。此外,抗菌肽通过刺激黏液合成增强胃粘膜屏障功能。总的来说,这些发现表明,抗菌肽作为一种潜在的天然抗生素在清除幽门螺杆菌和治疗慢性胃炎方面发挥着重要作用。
The antimicrobial peptide cathelicidin is critical for protection against different kinds of microbial infection. This study sought to elucidate the protective action of cathelicidin against Helicobacter pylori infection and its associated gastritis. Exogenous cathelicidin was found to inhibit H. pylori growth, destroy the bacteria biofilm, and induce morphological alterations in H. pylori membrane. Additionally, knockdown of endogenous cathelicidin in human gastric epithelial HFE-145 cells markedly increased the intracellular survival of H. pylori. Consistently, cathelicidin knockout mice exhibited stronger H. pylori colonization, higher expression of proinflammatory cytokines IL-6, IL-1β, and ICAM1, and lower expression of the anti-inflammatory cytokine IL-10 in the gastric mucosa upon H. pylori infection. In wild-type mice, H. pylori infection also stimulated gastric epithelium-derived cathelicidin production. Importantly, pretreatment with bioengineered Lactococcus lactis that actively secretes cathelicidin significantly increased mucosal cathelicidin levels and reduced H. pylori infection and the associated inflammation. Moreover, cathelicidin strengthened the barrier function of gastric mucosa by stimulating mucus synthesis. Collectively, these findings indicate that cathelicidin plays a significant role as a potential natural antibiotic for H. pylori clearance and a therapeutic agent for chronic gastritis.
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