Monocyte inflammation and adaptive immune dysfunction in severe Klebsiella pneumoniae pneumonia
13 affiliations
- 1National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and Prevention & Chinese Academy of Preventive Medicine Beijing China
- 2Department of Clinical Laboratory Shanxi Hospital of Traditional Chinese Medicine Taiyuan China
- 3NHC Key Laboratory of Pneumoconiosis, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Key Laboratory of Chronic Respiratory Diseases and Pneumoconiosis The First Hospital of Shanxi Medical University Taiyuan Shanxi China
- 4Research Center for Reverse Microbial Etiology, Workstation of Academician Shanxi Medical University Taiyuan People's Republic of China
- 5Ophthalmic Microbiology Laboratory, Shanxi Eye Hospital Shanxi Medical University Taiyuan Shanxi People's Republic of China
- 6Department of Internal Medicine, The First Clinical Medical College Shanxi Medical University Taiyuan Shanxi China
- 7School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Laboratory of Health Technology Assessment Fudan University Shanghai China
- 8Department of Laboratory Medicine First Hospital of Shanxi Medical University 85 Jiefang South Road Taiyuan Shanxi China
- 9Department of Respiratory and Critical Care Medicine Shanxi Hospital of Traditional Chinese Medicine Taiyuan China
- 10Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital Third Hospital of Shanxi Medical University Taiyuan China
- 11College of Pulmonary & Critical Care Medicine Chinese PLA General Hospital Beijing People's Republic of China
- 12Experimental Research Center & Molecular Diagnostic Center, Capital Center for Children's Health Capital Medical University, Capital Institute of Pediatrics Beijing People's Republic of China
- 13Beijing Research Center for Respiratory Infectious Diseases Beijing China
Abstract
Severe Klebsiella pneumoniae pneumonia is associated with substantial mortality and is characterized by intense systemic inflammation that coexists with a failure to control infection. The cellular changes underlying the transition from effective host defense to immune dysfunction remain incompletely defined. Here, we constructed a severity‐focused single‐cell transcriptomic atlas of 708,894 peripheral blood mononuclear cells from 100 individuals (54 healthy controls, 23 patients with mild disease, and 23 patients with severe disease), complemented by plasma protein measurements and flow cytometry. Mild disease was characterized by a relatively coordinated peripheral immune response, with preserved monocyte regulatory and tissue‐repair programs, preserved cytotoxic lymphocyte activity, and coordinated interactions between T follicular helper cells and B cells. Severe disease showed marked monocyte inflammation together with widespread disruption of adaptive immune responses. Classical monocytes expanded and showed increased expression of S100A8/A9/A12, accompanied by enhanced TLR4–MYD88 signaling and elevated plasma S100 proteins. These changes were accompanied by impaired dendritic cell antigen presentation, expansion of immunoregulatory monocyte states resembling monocytic myeloid‐derived suppressor cells, cytotoxicity‐ and exhaustion‐associated changes in CD8+ T cells and natural killer cells, hyperactivated yet poorly coordinated CD4+ T cell states, and weaker B cell receptor signaling despite plasma cell expansion. These findings delineate a severity‐associated peripheral immune state characterized by monocyte‐centered inflammatory signatures and features of altered adaptive immune coordination, and provide a basis for future mechanistic investigation of monocyte‐derived S100 alarmins and severity‐associated myeloid remodeling.
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BibTeX
@article{chen2026monocyte,
title = {{Monocyte inflammation and adaptive immune dysfunction in severe Klebsiella pneumoniae pneumonia}},
author = {Hongquan Chen and Xiaoling Wang and Xiang Liu and Kui Dong and Yanying Feng and Min Yuan and Shiyi Wang and Fangfang Fan and Yong Tian and Zhiming Kang and Xiushuai Du and Chaolu Hasi and Hong Lu and Wei Guan and Xu Chen and Mengyu Cheng and Wei Wei and Nan Guo and Zhiguo Liu and Xiaotong Qiu and Yiwei Shi and Kun Xiao and Yi Wang and Zhenjun Li},
journal = {iMeta},
year = {2026},
month = sep,
doi = {10.1002/imt2.70172},
url = {https://doi.org/10.1002/imt2.70172},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Monocyte inflammation and adaptive immune dysfunction in severe Klebsiella pneumoniae pneumonia
AU - Hongquan Chen
AU - Xiaoling Wang
AU - Xiang Liu
AU - Kui Dong
AU - Yanying Feng
AU - Min Yuan
AU - Shiyi Wang
AU - Fangfang Fan
AU - Yong Tian
AU - Zhiming Kang
AU - Xiushuai Du
AU - Chaolu Hasi
AU - Hong Lu
AU - Wei Guan
AU - Xu Chen
AU - Mengyu Cheng
AU - Wei Wei
AU - Nan Guo
AU - Zhiguo Liu
AU - Xiaotong Qiu
AU - Yiwei Shi
AU - Kun Xiao
AU - Yi Wang
AU - Zhenjun Li
PY - 2026
DA - 2026/09/21
JO - iMeta
DO - 10.1002/imt2.70172
UR - https://doi.org/10.1002/imt2.70172
AB - Severe Klebsiella pneumoniae pneumonia is associated with substantial mortality and is characterized by intense systemic inflammation that coexists with a failure to control infection. The cellular changes underlying the transition from effective host defense to immune dysfunction remain incompletely defined. Here, we constructed a severity‐focused single‐cell transcriptomic atlas of 708,894 peripheral blood mononuclear cells from 100 individuals (54 healthy controls, 23 patients with mild disease, and 23 patients with severe disease), complemented by plasma protein measurements and flow cytometry. Mild disease was characterized by a relatively coordinated peripheral immune response, with preserved monocyte regulatory and tissue‐repair programs, preserved cytotoxic lymphocyte activity, and coordinated interactions between T follicular helper cells and B cells. Severe disease showed marked monocyte inflammation together with widespread disruption of adaptive immune responses. Classical monocytes expanded and showed increased expression of S100A8/A9/A12, accompanied by enhanced TLR4–MYD88 signaling and elevated plasma S100 proteins. These changes were accompanied by impaired dendritic cell antigen presentation, expansion of immunoregulatory monocyte states resembling monocytic myeloid‐derived suppressor cells, cytotoxicity‐ and exhaustion‐associated changes in CD8+ T cells and natural killer cells, hyperactivated yet poorly coordinated CD4+ T cell states, and weaker B cell receptor signaling despite plasma cell expansion. These findings delineate a severity‐associated peripheral immune state characterized by monocyte‐centered inflammatory signatures and features of altered adaptive immune coordination, and provide a basis for future mechanistic investigation of monocyte‐derived S100 alarmins and severity‐associated myeloid remodeling.
SN - 2770-5986
SN - 2770-596X
ER -