Single-cell RNA sequencing dissects the immunosuppressive signatures in Helicobacter pylori-infected human gastric ecosystem
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<sup>+</sup> 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.
Authors
- Chong Bao (ORCID: https://orcid.org/0009-0000-0991-2848)
- Li Tan (ORCID: https://orcid.org/0000-0001-5961-0450)
- Zehua Wu (ORCID: https://orcid.org/0000-0001-7006-3232)
- Ping Zhou (ORCID: https://orcid.org/0000-0002-4394-2677)
- Si Lin Huang
- You Li (ORCID: https://orcid.org/0000-0002-3870-7031)
- Ze Min Chen
- William Ka Kei Wu (ORCID: https://orcid.org/0000-0002-5662-5240)
- Zhi Yong Zhai
- Gen Hua Yang
- Long Fei Li
- Xia Xi Li
- Lin Zhang
- Mei Ping Ou Yang
- Xiao Cui (ORCID: https://orcid.org/0009-0000-9302-9774)
- Chao Yang
- Wei Hu (ORCID: https://orcid.org/0000-0003-0209-8032)
- Ying Wang
- Wei Gong (ORCID: https://orcid.org/0000-0002-8568-0599)
- Gui Li Xia
- Yu Xuan Zhang
- Zhao Yu Huang
Institutions
- Chinese University of Hong Kong (HK)
- King's College London (GB)
- Third Affiliated Hospital of Southern Medical University (CN)
- Southern Medical University Shenzhen Hospital (CN)
- Shenzhen University Health Science Center (CN)
- Shenzhen Zhongshan Urological Hospital (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-25
- DOI
- https://doi.org/10.1038/s41467-025-59339-4
- Citations
- 16
- Primary Topic
- Helicobacter pylori-related gastroenterology studies
- Type
- article
- Field-Weighted Citation Impact
- 32.10
Funders
- Southern Medical University
- Shenzhen Hospital, Southern Medical University
- Basic and Applied Basic Research Foundation of Guangdong Province