Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, and Göteborg University Vaccine Research Institute (GUVAX) and the Mucosal Immunobiology and Vaccine Center (MIVAC), Göteborg, Sweden.
Infect Immun. 2013 Oct;81(10):3684-92. doi: 10.1128/IAI.00801-13. Epub 2013 Jul 22.
Infection with Helicobacter pylori is associated with development of ulcer disease and gastrointestinal adenocarcinoma. The infection leads to a large infiltration of immune cells and the formation of organized lymphoid follicles in the human gastric mucosa. Still, the immune system fails to eradicate the bacteria, and the substantial regulatory T cell (Treg) response elicited is probably a major factor permitting bacterial persistence. Dendritic cells (DCs) are professional antigen-presenting cells that can activate naive T cells, and maturation of DCs is crucial for the initiation of primary immune responses. The aim of this study was to investigate the presence and localization of mature human DCs in H. pylori-infected gastric mucosa. Gastric antral biopsy specimens were collected from patients with H. pylori-associated gastritis and healthy volunteers, and antrum tissue was collected from patients undergoing gastric resection. Immunohistochemistry and flow cytometry showed that DCs expressing the maturation marker dendritic cell lysosome-associated membrane glycoprotein (DC-LAMP; CD208) are enriched in the H. pylori-infected gastric mucosa and that these DCs are specifically localized within or close to lymphoid follicles. Gastric DC-LAMP-positive (DC-LAMP(+)) DCs express CD11c and high levels of HLA-DR but little CD80, CD83, and CD86. Furthermore, immunofluorescence analyses demonstrated that DC-LAMP(+) DCs are in the same location as FoxP3-positive putative Tregs in the follicles. In conclusion, we show that DC-LAMP(+) DCs with low costimulatory capacity accumulate in the lymphoid follicles in human H. pylori-infected gastric tissue, and our results suggest that Treg-DC interactions may promote chronic infection by rendering gastric DCs tolerogenic.
幽门螺杆菌感染与溃疡病和胃肠道腺癌的发展有关。该感染导致大量免疫细胞浸润和人类胃黏膜中淋巴滤泡的形成。然而,免疫系统未能清除细菌,而引发的大量调节性 T 细胞(Treg)反应可能是允许细菌持续存在的主要因素。树突状细胞(DCs)是能够激活初始 T 细胞的专业抗原呈递细胞,而 DCs 的成熟对于启动初级免疫反应至关重要。本研究旨在研究成熟人 DCs 在幽门螺杆菌感染胃黏膜中的存在和定位。从幽门螺杆菌相关性胃炎患者和健康志愿者中收集胃窦活检标本,并从接受胃切除术的患者中收集胃窦组织。免疫组织化学和流式细胞术显示,表达成熟标志物树突状细胞溶酶体相关膜糖蛋白(DC-LAMP;CD208)的 DCs 在幽门螺杆菌感染的胃黏膜中丰富存在,并且这些 DCs特异性定位于淋巴滤泡内或附近。胃 DC-LAMP 阳性(DC-LAMP(+))DCs表达 CD11c 和高水平的 HLA-DR,但表达很少的 CD80、CD83 和 CD86。此外,免疫荧光分析表明,DC-LAMP(+) DCs 与滤泡中 FoxP3 阳性的潜在 Treg 位于同一位置。总之,我们表明,具有低共刺激能力的 DC-LAMP(+) DCs 在人类幽门螺杆菌感染胃组织的淋巴滤泡中聚集,我们的结果表明,Treg-DC 相互作用可能通过使胃 DCs 耐受来促进慢性感染。
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