Background Helicobacter pylori typically colonizes the human stomach, but it can occasionally be detected in the oral cavity of infected persons. Clinical outcome as a result of gastric colonization depends on presence of the pathogenicity island cagPAI that encodes a type-IV secretion system (T4SS) for translocation of the effector protein CagA and ADP-heptose. Upon injection into target cells, CagA is phosphorylated, which can be demonstrated by in vitro infection of the gastric epithelial cell line AGS, resulting in cell elongation. Here we investigated whether H. pylori can exert these responses during interaction with cells from the oral epithelium. To this purpose, three oral epithelial cell lines, HN, CAL-27 and BHY, were infected with various virulent wild-type H. pylori strains, and CagA delivery and ADP-heptose-mediated pro-inflammatory responses were monitored. Results All three oral cell lines were resistant to elongation upon infection, despite similar bacterial binding capabilities. Moreover, T4SS-dependent CagA injection was absent. Resistance to CagA delivery was shown to be due to absence of CEACAM expression in these cell lines, while these surface molecules have recently been recognized as H. pylori T4SS receptors. Lack of CEACAM expression in HN, CAL-27 and BHY cells was overcome by genetic introduction of either CEACAM1, CEACAM5, or CEACAM6, which in each of the cell lines was proven sufficient to facilitate CagA delivery and phosphorylation upon H. pylori infection to levels similar to those observed with the gastric AGS cells. Pro-inflammatory responses, as measured by interleukin-8 ELISA, were induced to high levels in each cell line and CEACAM-independent. Conclusions These results show that lack of CEACAM receptors on the surface of the oral epithelial cells was responsible for resistance to H. pylori CagA-dependent pathogenic activities, and confirms the important role for the T4SS-dependent interaction of these receptors with H. pylori in the gastric epithelium.

中文翻译：

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CEACAM 受体表达的缺失阻止了幽门螺杆菌 CagA 向口腔上皮细胞的 IV 型分泌。

背景 幽门螺杆菌通常在人的胃中定殖，但偶尔可以在感染者的口腔中检测到。胃定植导致的临床结果取决于致病性岛 cagPAI 的存在，它编码用于效应蛋白 CagA 和 ADP-庚糖易位的 IV 型分泌系统 (T4SS)。注射到靶细胞后，CagA 被磷酸化，这可以通过胃上皮细胞系 AGS 的体外感染来证明，导致细胞伸长。在这里，我们研究了幽门螺杆菌是否可以在与口腔上皮细胞相互作用期间发挥这些反应。为此目的，三种口腔上皮细胞系 HN、CAL-27 和 BHY 被各种有毒的野生型幽门螺杆菌感染，并监测 CagA 递送和 ADP-庚糖介导的促炎反应。结果尽管细菌结合能力相似，但所有三种口腔细胞系都对感染后的伸长具有抗性。此外，没有 T4SS 依赖性 CagA 注射。对 CagA 递送的抗性被证明是由于这些细胞系中缺乏 CEACAM 表达，而这些表面分子最近被认为是幽门螺杆菌 T4SS 受体。通过基因导入 CEACAM1、CEACAM5 或 CEACAM6 克服了 HN、CAL-27 和 BHY 细胞中 CEACAM 表达不足的问题，在每种细胞系中，CEACAM6 已被证明足以促进 CagA 递送和 H. pylori 感染后的磷酸化水平与用胃 AGS 细胞观察到的相似。通过白细胞介素 8 ELISA 测量的促炎反应，在每个细胞系中被诱导至高水平并且不依赖 CEACAM。结胃上皮。