Single-cell RNA sequencing dissects the immunosuppressive signatures in Helicobacter pylori-infected human gastric ecosystem

Wei Hu, Ze Min Chen, Ying Wang, Chao Yang, Zi Ying Wu, Li Juan You, Zhi Yong Zhai, Zhao Yu Huang, Ping Zhou, Si Lin Huang, Xia Xi Li, Gen Hua Yang, Chong Ju Bao, Xiao Bing Cui, Gui Li Xia, Mei Ping Ou Yang, Lin Zhang, William Ka Kei Wu, Long Fei Li, Li Kai Tan, Yu Xuan Zhang and Wei Gong ()
Additional contact information
Wei Hu: Shenzhen
Ze Min Chen: The Chinese University of Hong Kong
Ying Wang: Shenzhen
Chao Yang: Shenzhen
Zi Ying Wu: Shenzhen
Li Juan You: Shenzhen
Zhi Yong Zhai: Shenzhen
Zhao Yu Huang: Shenzhen
Ping Zhou: Shenzhen
Si Lin Huang: Shenzhen
Xia Xi Li: Shenzhen
Gen Hua Yang: Shenzhen
Chong Ju Bao: Shenzhen
Xiao Bing Cui: Shenzhen
Gui Li Xia: Shenzhen
Mei Ping Ou Yang: Shenzhen
Lin Zhang: The Chinese University of Hong Kong
William Ka Kei Wu: The Chinese University of Hong Kong
Long Fei Li: Shenzhen
Li Kai Tan: The Chinese University of Hong Kong
Yu Xuan Zhang: King’s College London
Wei Gong: Shenzhen

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-59339-4

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