Objective Helicobacter pylori causes life-long colonisation of the gastric mucosa, leading to chronic inflammation with increased risk of gastric cancer. Research on the pathogenesis of this infection would strongly benefit from an authentic human in vitro model. Design Antrum-derived gastric glands from surgery specimens served to establish polarised epithelial monolayers via a transient air–liquid interface culture stage to study cross-talk with H. pylori and the adjacent stroma. Results The resulting ‘mucosoid cultures’, so named because they recapitulate key characteristics of the gastric mucosa, represent normal stem cell-driven cultures that can be passaged for months. These highly polarised columnar epithelial layers encompass the various gastric antral cell types and secrete mucus at the apical surface. By default, they differentiate towards a foveolar, MUC5AC-producing phenotype, whereas Wnt signalling stimulates proliferation of MUC6-producing cells and preserves stemness—reminiscent of the gland base. Stromal cells from the lamina propria secrete Wnt inhibitors, antagonising stem-cell niche signalling and inducing differentiation. On infection with H. pylori, a strong inflammatory response is induced preferentially in the undifferentiated basal cell phenotype. Infection of cultures for several weeks produces foci of viable bacteria and a persistent inflammatory condition, while the secreted mucus establishes a barrier that only few bacteria manage to overcome. Conclusion Gastric mucosoid cultures faithfully reproduce the features of normal human gastric epithelium, enabling new approaches for investigating the interaction of H. pylori with the epithelial surface and the cross-talk with the basolateral stromal compartment. Our observations provide striking insights in the regulatory circuits of inflammation and defence.

中文翻译：

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胃粘膜的极化上皮单层揭示了对粘膜稳态和防御感染的见解

目的幽门螺杆菌导致胃黏膜终生定植，导致慢性炎症，增加胃癌风险。对这种感染的发病机制的研究将极大地受益于真实的人类体外模型。设计来自手术标本的胃窦来源的胃腺通过短暂的气液界面培养阶段建立极化上皮单层，以研究与幽门螺杆菌和相邻基质的串扰。结果由此产生的“黏液样培养物”之所以如此命名是因为它们概括了胃黏膜的关键特征，代表了可以传代数月的正常干细胞驱动的培养物。这些高度极化的柱状上皮层包含各种胃窦细胞类型并在顶端表面分泌粘液。默认，它们向小凹、产生 MUC5AC 的表型分化，而 Wnt 信号刺激产生 MUC6 的细胞增殖并保持干性——让人联想到腺体底部。来自固有层的基质细胞分泌 Wnt 抑制剂，拮抗干细胞生态位信号并诱导分化。感染幽门螺杆菌后，未分化的基底细胞表型优先诱导强烈的炎症反应。培养物感染数周会产生活细菌的病灶和持续的炎症，而分泌的粘液建立了一个只有少数细菌能够克服的屏障。结论 胃黏液培养物忠实地再现了正常人胃上皮的特征，为研究幽门螺杆菌相互作用提供了新方法。pylori 与上皮表面和与基底外侧间质室的串扰。我们的观察为炎症和防御的调节回路提供了惊人的见解。