Early NK-cell and T-cell dysfunction marks progression to severe dengue in patients with obesity and healthy weight
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 a...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60941-9 |
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| Summary: | 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. |
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| ISSN: | 2041-1723 |