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

Author

Listed:
  • Wei Hu

    (Shenzhen
    Shenzhen)

  • Ze Min Chen

    (The Chinese University of Hong Kong)

  • Ying Wang

    (Shenzhen
    Shenzhen)

  • Chao Yang

    (Shenzhen
    Shenzhen)

  • Zi Ying Wu

    (Shenzhen
    Shenzhen)

  • Li Juan You

    (Shenzhen)

  • Zhi Yong Zhai

    (Shenzhen
    Shenzhen)

  • Zhao Yu Huang

    (Shenzhen
    Shenzhen)

  • Ping Zhou

    (Shenzhen
    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
    Shenzhen)

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.

Suggested Citation

  • 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 Xi, 2025. "Single-cell RNA sequencing dissects the immunosuppressive signatures in Helicobacter pylori-infected human gastric ecosystem," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59339-4
    DOI: 10.1038/s41467-025-59339-4
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