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Early NK-cell and T-cell dysfunction marks progression to severe dengue in patients with obesity and healthy weight

Author

Listed:
  • Michaela Gregorova

    (University of Bristol)

  • Marianna Santopaolo

    (University of Bristol)

  • Lucy C. Garner

    (University of Oxford)

  • Rahma F. Hayati

    (University of Bristol)

  • Divya Diamond

    (University of Bristol)

  • Narayan Ramamurthy

    (University of Oxford)

  • Vi Thuy Tran

    (Oxford University Clinical Research Unit)

  • Nguyet Minh Nguyen

    (Oxford University Clinical Research Unit)

  • Kate J. Heesom

    (University of Bristol)

  • Vuong Lam Nguyen

    (Oxford University Clinical Research Unit
    University of Medicine and Pharmacy at Ho Chi Minh City)

  • Eben Jones

    (University of Bristol)

  • Mike Nsubuga

    (University of Bristol)

  • Curtis Luscombe

    (University of Bristol)

  • Hoa Thi My Vo

    (Oxford University Clinical Research Unit)

  • Chanh Quang Ho

    (Oxford University Clinical Research Unit)

  • Chau Thi Xuan Nguyen

    (Oxford University Clinical Research Unit)

  • Tam Thi Hoai Dong

    (Oxford University Clinical Research Unit)

  • Duyen Thi Le Huynh

    (Oxford University Clinical Research Unit)

  • Tam Thi Cao

    (Hospital for Tropical Diseases)

  • Andrew D. Davidson

    (University of Bristol)

  • Paul Klenerman

    (University of Oxford
    Oxford University Hospitals NHS Foundation Trust)

  • Sophie Yacoub

    (Oxford University Clinical Research Unit
    Oxford University)

  • Laura Rivino

    (University of Bristol)

Abstract

Dengue is a mosquito-borne virus infection affecting half of the world’s population for which therapies are lacking. The role of T and NK-cells in protection/immunopathogenesis remains unclear for dengue. We performed a longitudinal phenotypic, functional and transcriptional analyses of T and NK-cells in 124 dengue patients using flow cytometry and single-cell RNA-sequencing. We show that T/NK-cell signatures early in infection discriminate patients who develop severe dengue (SD) from those who do not. These signatures are exacerbated in patients with overweight/obesity compared to healthy weight patients, supporting their increased susceptibility to SD. In SD, CD4+/CD8+ T-cells and NK-cells display increased co-inhibitory receptor expression and decreased cytotoxic potential compared to non-SD. Using transcriptional and proteomics approaches we show decreased type-I Interferon responses in SD, suggesting defective innate immunity may underlie NK/T-cell dysfunction. We propose that dysfunctional T and NK-cell signatures underpin dengue pathogenesis and may represent novel targets for immunomodulatory therapy in dengue.

Suggested Citation

  • Michaela Gregorova & Marianna Santopaolo & Lucy C. Garner & Rahma F. Hayati & Divya Diamond & Narayan Ramamurthy & Vi Thuy Tran & Nguyet Minh Nguyen & Kate J. Heesom & Vuong Lam Nguyen & Eben Jones & , 2025. "Early NK-cell and T-cell dysfunction marks progression to severe dengue in patients with obesity and healthy weight," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60941-9
    DOI: 10.1038/s41467-025-60941-9
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