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Updated: Oct 7, 2026
Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice
Published on: March 17, 2014
Dynamic orchestration of structural and immune cells in acute Pseudomonas aeruginosa pneumonia revealed by
Fuliang Zong1, Yan Wang1, Lingfei Hu1
1State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
Background:
Pseudomonas aeruginosa pneumonia triggers a complex, dynamic host response, yet the cellular coordination of inflammation and repair remains poorly defined.
Methods:
We performed time-resolved single-cell RNA sequencing (scRNA-seq) on murine lungs across five timepoints (0-96 h post-infection) and integrated these data with spatial transcriptomics (10x Visium) performed on matched tissue sections at key timepoints (0, 24, and 96 h), profiling a total of 41,452 high-quality cells.
Results:
We identified four neutrophil subsets, with the N3 population exhibiting potent antimicrobial activity. We traced the emergence of inflammatory fibroblasts during acute infection to Col13a1+ matrix fibroblasts, a process driven by a regulatory network centered on Stat1 and Nfkb1. Spatial transcriptomics with RCTD deconvolution revealed a 22.5% peak immune infiltration at 24 h, while COMMOT analysis uncovered 30-fold and 25-fold increases in Ccl2-Ccr2 and Cxcl2-Cxcr2 spatial signaling, respectively, pinpointing chemokine-driven recruitment foci. Notably, spatial mapping distinguished tissue remodeling activity from cell-type abundance, identifying acute matrix remodeling zones dominated by Timp1 rather than canonical fibroblast markers. Alveolar type 2 epithelial cells transitioned through three distinct states-homeostatic, inflammatory, and reparative. Notably, the circadian gene Dbp was specifically upregulated at 96 h, suggesting a role for circadian programs in resolution of pathology. Crucially, we uncovered a pivotal role for group 2 innate lymphoid cells (ILC2s): epithelial-derived IL-33 activated ILC2s via the ST2 receptor (Il1rl1) during acute infection (24 hpi), promoting a type 2 immune response that limits immunopathology.
Conclusion:
Our integrative time-resolved spatial transcriptomic atlas elucidates how structural and immune cells orchestrate the balance between bacterial clearance and tissue repair, highlighting novel targets for host-directed therapies in P. aeruginosa pneumonia.
