Single-cell transcriptomic atlas uncovers immune/structural lineage remodeling and fibrosis in Klebsiella pneumoniae-infected porcine lungs.
4 affiliations
- 1State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China.
- 2MOE Key Laboratory of Contemporary Anthropology, College of Life Sciences, Fudan University, Shanghai, China.
- 3State Key Laboratory for Animal Disease Control and Prevention, National Poultry Laboratory Animal Resource Center, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
- 4Department of Applied Biomedical Science, Faculty of Health Sciences, Mater Dei Hospital, University of Malta, Msida, Malta.
Abstract
Klebsiella pneumoniae (KP) is a predominant pathogen in respiratory infections, whose widespread antibiotic resistance poses severe public health risks and economic burdens. As the primary target of KP infection, the lung contains diverse immune cells, while pulmonary cellular responses to KP remain poorly understood. This study integrated single-cell RNA sequencing, flow cytometry, RT-qPCR, and immunofluorescence to investigate porcine lung cell response from healthy pigs and those infected with multidrug-resistant, highly virulent KP. Post-infection, myeloid cells (neutrophils, monocytes, and interstitial macrophages) were rapidly activated with upregulated signatures related to neutrophil migration and interferon production. Alveolar macrophages (AM) exhibited marked heterogeneity: KP infection was associated with apoptosis in proliferating, monocyte-derived, and tissue-resident AM subsets, indicating a disruption of homeostasis, while infection-specific subsets (AM_MHCII, AM_CXCL2) displayed enhanced antigen presentation, inflammatory activity, and pro-fibrotic potential. Under homeostasis, γδ T and CD8αα⁺ T cells were the predominant T cell populations. After infection, CX3CR1⁻CD8αα⁺ T cells were activated, and CD8⁺ γδ T cells increased their interactions with myeloid cells, predominantly through ligand-receptor pairs such as TNF-TNFRSF1B and IFNG-IFNGR1/2. Furthermore, KP induced lung fibroblast proliferation and activation via the ROS-mediated TGF-β/SMAD pathway, WNT pathway, and aerobic glycolysis. Concurrently, infection reduced the proportion of ATII and transitional AT0 cells, which may impair their differentiation into ATI cells and compromise epithelial barrier function. Thus, this study is the first to characterize the dynamics of KP infection in porcine lungs at single-cell resolution. It advances our understanding of KP-host interactions and provides a framework for anti-KP therapeutic development.
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BibTeX
@article{wang2026singlecell,
title = {{Single-cell transcriptomic atlas uncovers immune/structural lineage remodeling and fibrosis in Klebsiella pneumoniae-infected porcine lungs.}},
author = {Wei Wang and Junhui Zhu and Sibo Zhu and Changyou Xia and Xuan Jiang and Chuntong Bao and Ziheng Li and Rining Zhu and Tong Wu and Nan Zhang and Qila Sa and Shaopeng Wei and Brendon Scicluna and Fengyang Li and Liancheng Lei and Na Li},
journal = {Virulence},
year = {2026},
month = oct,
doi = {10.1080/21505594.2026.2747487},
url = {https://europepmc.org/article/MED/42862716},
note = {CC BY},
}
RIS
TY - JOUR
TI - Single-cell transcriptomic atlas uncovers immune/structural lineage remodeling and fibrosis in Klebsiella pneumoniae-infected porcine lungs.
AU - Wei Wang
AU - Junhui Zhu
AU - Sibo Zhu
AU - Changyou Xia
AU - Xuan Jiang
AU - Chuntong Bao
AU - Ziheng Li
AU - Rining Zhu
AU - Tong Wu
AU - Nan Zhang
AU - Qila Sa
AU - Shaopeng Wei
AU - Brendon Scicluna
AU - Fengyang Li
AU - Liancheng Lei
AU - Na Li
PY - 2026
DA - 2026/10/19
JO - Virulence
DO - 10.1080/21505594.2026.2747487
UR - https://europepmc.org/article/MED/42862716
AB - Klebsiella pneumoniae (KP) is a predominant pathogen in respiratory infections, whose widespread antibiotic resistance poses severe public health risks and economic burdens. As the primary target of KP infection, the lung contains diverse immune cells, while pulmonary cellular responses to KP remain poorly understood. This study integrated single-cell RNA sequencing, flow cytometry, RT-qPCR, and immunofluorescence to investigate porcine lung cell response from healthy pigs and those infected with multidrug-resistant, highly virulent KP. Post-infection, myeloid cells (neutrophils, monocytes, and interstitial macrophages) were rapidly activated with upregulated signatures related to neutrophil migration and interferon production. Alveolar macrophages (AM) exhibited marked heterogeneity: KP infection was associated with apoptosis in proliferating, monocyte-derived, and tissue-resident AM subsets, indicating a disruption of homeostasis, while infection-specific subsets (AM_MHCII, AM_CXCL2) displayed enhanced antigen presentation, inflammatory activity, and pro-fibrotic potential. Under homeostasis, γδ T and CD8αα⁺ T cells were the predominant T cell populations. After infection, CX3CR1⁻CD8αα⁺ T cells were activated, and CD8⁺ γδ T cells increased their interactions with myeloid cells, predominantly through ligand-receptor pairs such as TNF-TNFRSF1B and IFNG-IFNGR1/2. Furthermore, KP induced lung fibroblast proliferation and activation via the ROS-mediated TGF-β/SMAD pathway, WNT pathway, and aerobic glycolysis. Concurrently, infection reduced the proportion of ATII and transitional AT0 cells, which may impair their differentiation into ATI cells and compromise epithelial barrier function. Thus, this study is the first to characterize the dynamics of KP infection in porcine lungs at single-cell resolution. It advances our understanding of KP-host interactions and provides a framework for anti-KP therapeutic development.
SN - 2150-5594
SN - 2150-5608
ER -