A pan-immune panorama of bacterial pneumonia revealed by a large-scale single-cell transcriptome atlas.

Xiao, K; Cao, Y; Han, Z; Zhang, Y; Luu, LDW; Chen, L; Yan, P; Chen, W; Wang, J; Liang, Y; Shi, X; Wang, X; Wang, F; Hu, Y; Wen, Z; Chen, Y; Yang, Y; Yu, H; Xie, L; Wang, Y

A pan-immune panorama of bacterial pneumonia revealed by a large-scale single-cell transcriptome atlas.

Xiao, K Cao, Y Han, Z Zhang, Y Luu, LDW Chen, L Yan, P Chen, W Wang, J Liang, Y Shi, X Wang, X Wang, F Hu, Y Wen, Z Chen, Y Yang, Y Yu, H Xie, L Wang, Y

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Publisher:: SPRINGERNATURE
Publication Type:: Journal Article
Citation:: Signal Transduct Target Ther, 2025, 10, (1), pp. 5
Issue Date:: 2025-01-06

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Field	Value	Language
dc.contributor.author	Xiao, K
dc.contributor.author	Cao, Y
dc.contributor.author	Han, Z
dc.contributor.author	Zhang, Y
dc.contributor.author	Luu, LDW
dc.contributor.author	Chen, L
dc.contributor.author	Yan, P
dc.contributor.author	Chen, W
dc.contributor.author	Wang, J
dc.contributor.author	Liang, Y
dc.contributor.author	Shi, X
dc.contributor.author	Wang, X
dc.contributor.author	Wang, F
dc.contributor.author	Hu, Y
dc.contributor.author	Wen, Z
dc.contributor.author	Chen, Y
dc.contributor.author	Yang, Y
dc.contributor.author	Yu, H
dc.contributor.author	Xie, L
dc.contributor.author	Wang, Y
dc.date.accessioned	2025-07-15T05:28:16Z
dc.date.available	2024-12-06
dc.date.available	2025-07-15T05:28:16Z
dc.date.issued	2025-01-06
dc.identifier.citation	Signal Transduct Target Ther, 2025, 10, (1), pp. 5
dc.identifier.issn	2095-9907
dc.identifier.issn	2059-3635
dc.identifier.uri	http://hdl.handle.net/10453/188227
dc.description.abstract	Bacterial pneumonia is a significant public health burden, contributing to substantial morbidity, mortality, and healthcare costs. Current therapeutic strategies beyond antibiotics and adjuvant therapies are limited, highlighting the need for a deeper understanding of the disease pathogenesis. Here, we employed single-cell RNA sequencing of 444,146 bronchoalveolar lavage fluid cells (BALFs) from a large cohort of 74 individuals, including 58 patients with mild (n = 22) and severe (n = 36) diseases as well as 16 healthy donors. Enzyme-linked immunosorbent and histological assays were applied for validation within this cohort. The heterogeneity of immune responses in bacterial pneumonia was observed, with distinct immune cell profiles related to disease severity. Severe bacterial pneumonia was marked by an inflammatory cytokine storm resulting from systemic upregulation of S100A8/A9 and CXCL8, primarily due to specific macrophage and neutrophil subsets. In contrast, mild bacterial pneumonia exhibits an effective humoral immune response characterized by the expansion of T follicular helper and T helper 2 cells, facilitating B cell activation and antibody production. Although both disease groups display T cell exhaustion, mild cases maintained robust cytotoxic CD8+T cell function, potentially reflecting a compensatory mechanism. Dysregulated neutrophil and macrophage responses contributed significantly to the pathogenesis of severe disease. Immature neutrophils promote excessive inflammation and suppress T cell activation, while a specific macrophage subset (Macro_03_M1) displaying features akin to myeloid-derived suppressor cells (M-MDSCs) suppress T cells and promote inflammation. Together, these findings highlight potential therapeutic targets for modulating immune responses and improving clinical outcomes in bacterial pneumonia.
dc.format	Electronic
dc.language	eng
dc.publisher	SPRINGERNATURE
dc.relation.ispartof	Signal Transduct Target Ther
dc.relation.isbasedon	10.1038/s41392-024-02093-8
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	3101 Biochemistry and cell biology
dc.subject.mesh	Humans
dc.subject.mesh	Pneumonia, Bacterial
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Transcriptome
dc.subject.mesh	Single-Cell Analysis
dc.subject.mesh	Calgranulin A
dc.subject.mesh	Calgranulin B
dc.subject.mesh	Middle Aged
dc.subject.mesh	Interleukin-8
dc.subject.mesh	Bronchoalveolar Lavage Fluid
dc.subject.mesh	Aged
dc.subject.mesh	Neutrophils
dc.subject.mesh	Adult
dc.subject.mesh	Macrophages
dc.subject.mesh	Neutrophils
dc.subject.mesh	Macrophages
dc.subject.mesh	Bronchoalveolar Lavage Fluid
dc.subject.mesh	Humans
dc.subject.mesh	Pneumonia, Bacterial
dc.subject.mesh	Calgranulin A
dc.subject.mesh	Calgranulin B
dc.subject.mesh	Interleukin-8
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Single-Cell Analysis
dc.subject.mesh	Transcriptome
dc.subject.mesh	Humans
dc.subject.mesh	Pneumonia, Bacterial
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Transcriptome
dc.subject.mesh	Single-Cell Analysis
dc.subject.mesh	Calgranulin A
dc.subject.mesh	Calgranulin B
dc.subject.mesh	Middle Aged
dc.subject.mesh	Interleukin-8
dc.subject.mesh	Bronchoalveolar Lavage Fluid
dc.subject.mesh	Aged
dc.subject.mesh	Neutrophils
dc.subject.mesh	Adult
dc.subject.mesh	Macrophages
dc.title	A pan-immune panorama of bacterial pneumonia revealed by a large-scale single-cell transcriptome atlas.
dc.type	Journal Article
utslib.citation.volume	10
utslib.location.activity	England
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2025-07-15T05:28:13Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	10
utslib.citation.issue	1

Abstract:

Bacterial pneumonia is a significant public health burden, contributing to substantial morbidity, mortality, and healthcare costs. Current therapeutic strategies beyond antibiotics and adjuvant therapies are limited, highlighting the need for a deeper understanding of the disease pathogenesis. Here, we employed single-cell RNA sequencing of 444,146 bronchoalveolar lavage fluid cells (BALFs) from a large cohort of 74 individuals, including 58 patients with mild (n = 22) and severe (n = 36) diseases as well as 16 healthy donors. Enzyme-linked immunosorbent and histological assays were applied for validation within this cohort. The heterogeneity of immune responses in bacterial pneumonia was observed, with distinct immune cell profiles related to disease severity. Severe bacterial pneumonia was marked by an inflammatory cytokine storm resulting from systemic upregulation of S100A8/A9 and CXCL8, primarily due to specific macrophage and neutrophil subsets. In contrast, mild bacterial pneumonia exhibits an effective humoral immune response characterized by the expansion of T follicular helper and T helper 2 cells, facilitating B cell activation and antibody production. Although both disease groups display T cell exhaustion, mild cases maintained robust cytotoxic CD8+T cell function, potentially reflecting a compensatory mechanism. Dysregulated neutrophil and macrophage responses contributed significantly to the pathogenesis of severe disease. Immature neutrophils promote excessive inflammation and suppress T cell activation, while a specific macrophage subset (Macro_03_M1) displaying features akin to myeloid-derived suppressor cells (M-MDSCs) suppress T cells and promote inflammation. Together, these findings highlight potential therapeutic targets for modulating immune responses and improving clinical outcomes in bacterial pneumonia.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/188227