Single‐Cell Atlas Reveals Neutrophil Heterogeneity in Hypervirulent Klebsiella pneumoniae Infection‐Induced Sepsis
- 1Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences City University of Hong Kong Hong Kong China
- 2State Key Lab of Chemical Biology and Drug Discovery and the Department of Food Science and Nutrition The Hong Kong Polytechnic University Hong Kong China
Abstract
Hypervirulent Klebsiella pneumoniae (hvKp) infection often induces sepsis characterised by remarkable phenotypic and functional diversity among neutrophils. However, the roles of distinct lung neutrophil compartments involved in hvKp infection remain poorly understood. Here, utilising single‐cell RNA sequencing, we identified four neutrophil subsets in the lungs of hvKp‐infected mice: N1, N2, N3a, and N3b, which were organised along a maturation trajectory. Functionally, early‐stage subsets exhibited proinflammatory and phagocytic activities with high levels of activation, whereas terminal subsets displayed enhanced pathogen sensing and immunoregulatory properties. Notably, the N3b population showed pronounced immunosuppressive features and was predicted to inhibit lymphocyte responses through Lgals9 and Ceacam1 ligands, potentially associated with hvKp‐induced lymphopenia. Projection onto NeuMap further validated the functional states of identified subsets, linking N1 to proliferative programmes, N2 to granules and hypoxia‐associated metabolic activity, N3a to antigen‐presentation signatures and N3b to immunosuppressive hubs. Morphologically, N3a/b were predicted to be enriched for segmented neutrophils, consistent with a more mature phenotype compared with N1 and N2. Notably, segmented neutrophils were markedly expanded in infected lungs, suggesting their association with hvKp pathogenesis. Together, our findings delineate the lung neutrophil landscape in hvKp‐induced sepsis, providing insights for understanding hvKp pathogenesis and developing targeted therapeutic interventions at a neutrophil subset level.
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BibTeX
@article{fang2026singlecell,
title = {{Single‐Cell Atlas Reveals Neutrophil Heterogeneity in Hypervirulent Klebsiella pneumoniae Infection‐Induced Sepsis}},
author = {Xiang Fang and Weizhao Li and Xinyu Zhang and Sohana Akter Mina and Qianling Jiang and Gaochen Zhu and Sheng Chen and Guan Yang},
journal = {Immunology},
year = {2026},
month = aug,
doi = {10.1111/imm.70193},
url = {https://doi.org/10.1111/imm.70193},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single‐Cell Atlas Reveals Neutrophil Heterogeneity in Hypervirulent Klebsiella pneumoniae Infection‐Induced Sepsis
AU - Xiang Fang
AU - Weizhao Li
AU - Xinyu Zhang
AU - Sohana Akter Mina
AU - Qianling Jiang
AU - Gaochen Zhu
AU - Sheng Chen
AU - Guan Yang
PY - 2026
DA - 2026/08/27
JO - Immunology
DO - 10.1111/imm.70193
UR - https://doi.org/10.1111/imm.70193
AB - Hypervirulent Klebsiella pneumoniae (hvKp) infection often induces sepsis characterised by remarkable phenotypic and functional diversity among neutrophils. However, the roles of distinct lung neutrophil compartments involved in hvKp infection remain poorly understood. Here, utilising single‐cell RNA sequencing, we identified four neutrophil subsets in the lungs of hvKp‐infected mice: N1, N2, N3a, and N3b, which were organised along a maturation trajectory. Functionally, early‐stage subsets exhibited proinflammatory and phagocytic activities with high levels of activation, whereas terminal subsets displayed enhanced pathogen sensing and immunoregulatory properties. Notably, the N3b population showed pronounced immunosuppressive features and was predicted to inhibit lymphocyte responses through Lgals9 and Ceacam1 ligands, potentially associated with hvKp‐induced lymphopenia. Projection onto NeuMap further validated the functional states of identified subsets, linking N1 to proliferative programmes, N2 to granules and hypoxia‐associated metabolic activity, N3a to antigen‐presentation signatures and N3b to immunosuppressive hubs. Morphologically, N3a/b were predicted to be enriched for segmented neutrophils, consistent with a more mature phenotype compared with N1 and N2. Notably, segmented neutrophils were markedly expanded in infected lungs, suggesting their association with hvKp pathogenesis. Together, our findings delineate the lung neutrophil landscape in hvKp‐induced sepsis, providing insights for understanding hvKp pathogenesis and developing targeted therapeutic interventions at a neutrophil subset level.
SN - 0019-2805
SN - 1365-2567
ER -