Hu Wei, Chen Ze Min, Wang Ying, Yang Chao, Wu Zi Ying, You Li Juan, Zhai Zhi Yong, Huang Zhao Yu, Zhou Ping, Huang Si Lin, Li Xia Xi, Yang Gen Hua, Bao Chong Ju, Cui Xiao Bing, Xia Gui Li, Ou Yang Mei Ping, Zhang Lin, Wu William Ka Kei, Li Long Fei, Tan Li Kai, Zhang Yu Xuan, Gong Wei
Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China.
Nat Commun. 2025 Apr 25;16(1):3903. doi: 10.1038/s41467-025-59339-4.
Helicobacter pylori (H. pylori) manipulates the host immune system to establish a persistent colonization, posing a serious threat to human health, but the mechanisms remain poorly understood. Here we integrate single-cell RNA sequencing and TCR profiling for analyzing 187,192 cells from 11 H. pylori-negative and 12 H. pylori-positive individuals to describe the human gastric ecosystem reprogrammed by H. pylori infection, as manifested by impaired antigen presentation and phagocytosis function. We further delineate a monocyte-to-C1QC macrophage differentiation trajectory driven by H. pylori infection, while T cell responses exhibit broad functional impairment and hyporesponsiveness with restricted clonal expansion capacity. We also identify an HLA-DRs- and CTLA4-expressing T cell population residing in H. pylori-inhabited stomach that potentially contribute to immune evasion. Together, our findings provide single-cell resolution information into the immunosuppressive microenvironment shaped by H. pylori infection, offering critical insights for developing novel therapeutic approaches to eliminate this globally prevalent pathogen.
幽门螺杆菌（H. pylori）操控宿主免疫系统以建立持续定植，对人类健康构成严重威胁，但其机制仍知之甚少。在此，我们整合单细胞RNA测序和TCR分析，对来自11名幽门螺杆菌阴性和12名幽门螺杆菌阳性个体的187,192个细胞进行分析，以描述因幽门螺杆菌感染而重新编程的人类胃生态系统，表现为抗原呈递和吞噬功能受损。我们进一步描绘了由幽门螺杆菌感染驱动的单核细胞向C1QC巨噬细胞的分化轨迹，而T细胞反应表现出广泛的功能障碍和低反应性，克隆扩增能力受限。我们还鉴定出一群表达HLA-DRs和CTLA4的T细胞，它们存在于幽门螺杆菌定植的胃中，可能有助于免疫逃逸。总之，我们的研究结果为幽门螺杆菌感染形成的免疫抑制微环境提供了单细胞分辨率信息，为开发消除这种全球流行病原体的新型治疗方法提供了关键见解。
