Nature Communications (Apr 2025)

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,
  • Wei Gong

DOI
https://doi.org/10.1038/s41467-025-59339-4
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 16

Abstract

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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.