Cheng Liu, Mirko Rossi, Sara Lindén, Medea Padra, Caroline Blaecher, Eva Bauwens, Myrthe Joosten, Bram Flahou, Wim Van den Broeck, Richard Ducatelle, Freddy Haesebrouck, Annemieke Smet
Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Helicobacter. 2016 Dec;21(6):504-522. doi: 10.1111/hel.12307. Epub 2016 Mar 3.
Helicobacter 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.
Bacterial hof gene and host gene expression experiments, Helicobacter binding assays and experimental infection studies in mice were performed. H. pylori and its ΔhofF mutant were included for comparison.
Helicobacter 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 ΔhofE and ΔhofF and H. pylori ΔhofF 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-1β 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.
These 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-1β-induced gastric MUC13/Muc13 expression.
海尔曼幽门螺杆菌是一种与人类胃部疾病相关的人畜共患细菌。我们最近发现，海尔曼幽门螺杆菌可与人胃粘蛋白和上皮细胞结合，并强调了小鼠Muc13粘蛋白在胃部幽门螺杆菌定植中的潜在作用。本研究的目的是探讨编码HofH/F/E/G/C/D的海尔曼幽门螺杆菌hof基因座在粘附胃黏膜及诱导胃Muc13表达增加中的作用。
进行了细菌hof基因和宿主基因表达实验、幽门螺杆菌结合试验以及小鼠实验性感染研究。纳入幽门螺杆菌及其ΔhofF突变体进行比较。
与海尔曼幽门螺杆菌野生型菌株相比，缺乏HofE或HofF的海尔曼幽门螺杆菌菌株在感染后4周和9周时，与胃粘蛋白和上皮细胞的结合明显减少，在Balb/c小鼠胃中的定植水平也较低。有趣的是，海尔曼幽门螺杆菌ΔhofE和ΔhofF以及幽门螺杆菌ΔhofF并未诱导人胃上皮细胞中MUC13以及小鼠胃中Muc13的表达增加。最后，我们证明，胃部对幽门螺杆菌定植的反应会诱导IL-1β产生，而IL-1β又参与胃上皮中MUC13/Muc13的表达。
幽门螺杆菌研究中的这些新结果确定海尔曼幽门螺杆菌HofE和HofF为粘附素，并表明海尔曼幽门螺杆菌HofE和HofF以及幽门螺杆菌HofF在IL-1β诱导的胃MUC13/Muc13表达中起重要作用。
