The Helicobacter heilmannii hofE and hofF Genes are Essential for Colonization of the Gastric Mucosa and Play a Role in IL-1-Induced Gastric MUC13 Expression

The Helicobacter heilmannii hofE and hofF Genes are Essential for Colonization of the Gastric Mucosa and Play a Role in IL-1-Induced Gastric MUC13 Expression
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DOI:
10.1111/hel.12307
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发表时间:
2016-12-01
期刊:
影响因子:
4.4
通讯作者:
Annemieke, Smet
Annemieke, Smet
中科院分区:
医学2区
文献类型:
--
作者:
Cheng, Liu;Mirko, Rossi;Annemieke, Smet

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研究背景海尔曼螺杆菌是一种与人类胃病相关的人畜共患细菌。我们最近发现H. Heilmannii与人胃粘蛋白和上皮细胞结合,并强调了鼠Muc 13粘蛋白在胃螺杆菌定殖中的潜在作用。本研究的目的是探讨H。方法采用细菌霍夫基因和宿主基因表达实验、幽门螺杆菌结合实验和小鼠实验感染研究。H.结果缺失霍费或霍夫的Helicobacterheilmannii菌株在感染后4周和9周时与胃粘蛋白和上皮细胞的结合明显减少,并且在Balb/c小鼠胃中的定植水平低于缺失HofF的Helicobacterheilmannii菌株。海尔曼野生型菌株。有趣的是,H。heilmannii霍费和霍夫和H. pylori霍夫没有诱导人胃上皮细胞中MUC 13和小鼠胃中MUC 13的表达增加。最后,我们证明,IL-1是诱导在胃中作为一个响应螺杆菌定植,这反过来又参与了MUC 13/MUC 13在胃上皮的表达。heilmannii霍费和霍夫作为粘附素,提示H. heilmannii霍费霍夫和H. pylori霍夫在IL-1诱导的胃粘膜MUC 13/Muc 13表达中的作用。
BackgroundHelicobacter heilmannii is a zoonotic bacterium associated with gastric disease in humans. We recently showed that H. heilmannii binds to human gastric mucins and epithelial cells and highlighted a potential role for the murine Muc13 mucin in gastric Helicobacter colonization. The aims of this study were to investigate the role of the H. heilmannii hof gene locus encoding HofH/F/E/G/C/D in adhesion to the gastric mucosa and induction of increased gastric Muc13 expression.MethodsBacterial hof gene and host gene expression experiments, Helicobacter binding assays and experimental infection studies in mice were performed. H. pylori and its hofF mutant were included for comparison.ResultsHelicobacter heilmannii strains lacking HofE or HofF showed a clear decrease in binding to gastric mucins and epithelial cells as well as a lower gastric colonization level in the stomach of Balb/c mice at 4 and 9 weeks post-infection compared to the H. heilmannii wildtype strain. Interestingly, H. heilmannii hofE and hofF and H. pylori hofF did not induce an increased expression of MUC13 in human gastric epithelial cells and of Muc13 in the stomach of mice. Finally, we demonstrated that IL-1 is induced in the stomach as a response to Helicobacter colonization which on its turn is involved in the expression of MUC13/Muc13 in the gastric epithelium.ConclusionThese novel results in Helicobacter research identified H. heilmannii HofE and HofF as adhesins and suggest an important role of H. heilmannii HofE and HofF and H. pylori HofF in IL-1-induced gastric MUC13/Muc13 expression.