A pan-immune panorama of bacterial pneumonia revealed by a large-scale single-cell transcriptome atlas
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 pathogenes...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-024-02093-8 |
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| author | Kun Xiao Yan Cao Zhihai Han Yuxiang Zhang Laurence Don Wai Luu Liang Chen Peng Yan Wei Chen Jiaxing Wang Ying Liang Xin Shi Xiuli Wang Fan Wang Ye Hu Zhengjun Wen Yong Chen Yuwei Yang Haotian Yu Lixin Xie Yi Wang |
| author_facet | Kun Xiao Yan Cao Zhihai Han Yuxiang Zhang Laurence Don Wai Luu Liang Chen Peng Yan Wei Chen Jiaxing Wang Ying Liang Xin Shi Xiuli Wang Fan Wang Ye Hu Zhengjun Wen Yong Chen Yuwei Yang Haotian Yu Lixin Xie Yi Wang |
| author_sort | Kun Xiao |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-9bfcdf04382e493cba51d13a357ca40a |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-9bfcdf04382e493cba51d13a357ca40a2025-01-12T12:41:37ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-01-0110111710.1038/s41392-024-02093-8A pan-immune panorama of bacterial pneumonia revealed by a large-scale single-cell transcriptome atlasKun Xiao0Yan Cao1Zhihai Han2Yuxiang Zhang3Laurence Don Wai Luu4Liang Chen5Peng Yan6Wei Chen7Jiaxing Wang8Ying Liang9Xin Shi10Xiuli Wang11Fan Wang12Ye Hu13Zhengjun Wen14Yong Chen15Yuwei Yang16Haotian Yu17Lixin Xie18Yi Wang19College of Pulmonary & Critical Care Medicine, The Eighth Medical Center of Chinese PLA General HospitalCollege of Pulmonary & Critical Care Medicine, The Eighth Medical Center of Chinese PLA General HospitalCollege of Pulmonary & Critical Care Medicine, The Eighth Medical Center of Chinese PLA General HospitalDepartment of Critical Care Medicine, The Eighth Medical Center of Chinese PLA General HospitalSchool of Life Sciences, University of Technology SydneyRespiratory and Critical Care Medicine department, Beijing Jingmei Group, General HospialDepartment of Pulmonary and Critical Care Medicine, China Aerospace Science & Industry Corporation 731 hospitalCollege of Pulmonary & Critical Care Medicine, The Eighth Medical Center of Chinese PLA General HospitalDepartment of Critical Care Medicine, The Eighth Medical Center of Chinese PLA General HospitalDepartment of Respiratory and Critical Care Medicine, Peking University Third HospitalCollege of Pulmonary & Critical Care Medicine, The Eighth Medical Center of Chinese PLA General HospitalCollege of Pulmonary & Critical Care Medicine, The Eighth Medical Center of Chinese PLA General HospitalCollege of Pulmonary & Critical Care Medicine, The Eighth Medical Center of Chinese PLA General HospitalCollege of Pulmonary & Critical Care Medicine, The Eighth Medical Center of Chinese PLA General HospitalRespiratory and Critical Care Medicine department, Beijing Jingmei Group, General HospialDepartment of Pulmonary and Critical Care Medicine, Anzhen hospital afflicted to Capital medical universityCollege of Pulmonary & Critical Care Medicine, The Eighth Medical Center of Chinese PLA General HospitalThe Eighth Medical Center of Chinese PLA General HospitalCollege of Pulmonary & Critical Care Medicine, The Eighth Medical Center of Chinese PLA General HospitalExperimental Research Center, Capital Institute of PediatricsAbstract 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.https://doi.org/10.1038/s41392-024-02093-8 |
| spellingShingle | Kun Xiao Yan Cao Zhihai Han Yuxiang Zhang Laurence Don Wai Luu Liang Chen Peng Yan Wei Chen Jiaxing Wang Ying Liang Xin Shi Xiuli Wang Fan Wang Ye Hu Zhengjun Wen Yong Chen Yuwei Yang Haotian Yu Lixin Xie Yi Wang A pan-immune panorama of bacterial pneumonia revealed by a large-scale single-cell transcriptome atlas Signal Transduction and Targeted Therapy |
| title | A pan-immune panorama of bacterial pneumonia revealed by a large-scale single-cell transcriptome atlas |
| title_full | A pan-immune panorama of bacterial pneumonia revealed by a large-scale single-cell transcriptome atlas |
| title_fullStr | A pan-immune panorama of bacterial pneumonia revealed by a large-scale single-cell transcriptome atlas |
| title_full_unstemmed | A pan-immune panorama of bacterial pneumonia revealed by a large-scale single-cell transcriptome atlas |
| title_short | A pan-immune panorama of bacterial pneumonia revealed by a large-scale single-cell transcriptome atlas |
| title_sort | pan immune panorama of bacterial pneumonia revealed by a large scale single cell transcriptome atlas |
| url | https://doi.org/10.1038/s41392-024-02093-8 |
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