ABSTRACT

Introduction: Campylobacter concisus is an oral bacterium that is associated with inflammatory bowel disease (IBD) and Barrett’s esophagus (BE). Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that is used by tumor cells for immune evasion and has increased expression in patients with IBD and BE. We examined whether C. concisus upregulates PD-L1 expression in intestinal and esophageal epithelial cells.

Methods: Human intestinal epithelial HT-29 cells and esophageal epithelial FLO-1 cells with and without interferon (IFN)-γ sensitization were incubated with C. concisus strains. The level of PD-L1 mRNA was quantified using quantitative real-time PCR. Cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Apoptosis of HT-29 and FLO-1 cells were measured using caspase 3/7 assay.

Results: We found that intestinal epithelial cells with IFN-γ sensitization incubated with C. concisus significantly upregulated PD-L1 expression and significantly increased the production of interleukin (IL)-8. Whereas, PD-L1 expression was significantly inhibited in IFN-γ sensitized FLO-1 cells incubated with C. concisus strains. Furthermore, FLO-1 cells with and without IFN-γ sensitization incubated with C. concisus strains both had significantly higher levels of cell death.

Conclusion: C. concisushas the potential to cause damage to both intestinal and esophageal epithelial cells, however, with different pathogenic effects.

 抽象的

简介： Conpylobacter concisus是一种口腔细菌，与炎症性肠病 (IBD) 和巴雷特食管 (BE) 相关。程序性细胞死亡配体-1 (PD-L1) 是一种免疫检查点蛋白，肿瘤细胞利用它来逃避免疫，并且在 IBD 和 BE 患者中表达增加。我们检查了C. concisus是否上调肠和食管上皮细胞中的 PD-L1 表达。

方法：将有或没有干扰素（IFN）-γ致敏的人肠上皮HT-29细胞和食管上皮FLO-1细胞与C. concisus菌株一起孵育。使用定量实时 PCR 对 PD-L1 mRNA 水平进行定量。使用酶联免疫吸附测定（ELISA）测量细胞因子。使用 caspase 3/7 测定法测量 HT-29 和 FLO-1 细胞的凋亡。

结果：我们发现，用 IFN-γ 致敏的肠上皮细胞与C. concisus一起孵育，显着上调 PD-L1 表达，并显着增加白细胞介素 (IL)-8 的产生。然而，在与C. concisus菌株一起孵育的 IFN-γ 致敏 FLO-1 细胞中，PD-L1 表达显着受到抑制。此外，与C. concisus菌株一起孵育的具有和不具有 IFN-γ 致敏作用的 FLO-1 细胞均具有显着更高水平的细胞死亡。

结论： C. concisus有可能对肠和食管上皮细胞造成损害，但致病作用不同。