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Transcriptomic responses of lung mesenchymal cells during pneumonia
Alicia M Soucy1, Jourdan E Brune2,3, Archana Jayaraman1
1Pulmonary Center, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Abstract:
The role of mesenchymal cells during respiratory infection is not well defined, including whether, which, and how the different types of mesenchymal cells respond. We collected all mesenchymal cells from lung single-cell suspensions of mice that were naive (after receiving only saline vehicle), pneumonic (after intratracheal instillation of pneumococcus 24 hours previously), or resolved from infection (after nonlethal pneumococcal infections 6 weeks previously) and performed single-cell RNA sequencing. Cells clustered into 5 well-separated groups based on their transcriptomes: matrix fibroblasts, myofibroblasts, pericytes, smooth muscle cells, and mesothelial cells. Fibroblasts were the most abundant and could be further segregated into Pdgfra+Npnt+Ces1d+Col13a1+ alveolar fibroblasts and Cd9+Pi16+Sca1+Col14a1+ adventitial fibroblasts. The cells from naive and resolved groups overlapped in dimension reduction plots, suggesting the mesenchymal cells returned to baseline transcriptomes after resolution. During pneumonia, all mesenchymal cells responded with altered transcriptomes, revealing a core response that had been conserved across cell types as well as distinct mesenchymal cell type-specific responses. The different subsets of fibroblasts induced similar gene sets, but the alveolar fibroblasts responded more strongly than the adventitial fibroblasts. These data demonstrated diverse and specialized immune activities of lung mesenchymal cells during pneumonia.
Insights
Lung mesenchymal cells show diverse immune activities during respiratory infections. Different fibroblast types respond uniquely, with alveolar fibroblasts showing a stronger response than adventitial fibroblasts.
Area of Science:
- Immunology
- Cell Biology
- Respiratory Medicine
Background:
- The function of mesenchymal cells in lung infections is poorly understood.
- Specific mesenchymal cell types and their responses during respiratory infections require clarification.
Purpose of the Study:
- To investigate the diverse roles and responses of lung mesenchymal cells during pneumococcal pneumonia.
- To characterize the transcriptomic changes in different mesenchymal cell subsets during infection and resolution.
Main Methods:
- Single-cell RNA sequencing was performed on lung mesenchymal cells from mice in naive, pneumonic, and resolved infection states.
- Mesenchymal cells were classified into distinct subtypes including fibroblasts, myofibroblasts, pericytes, smooth muscle cells, and mesothelial cells.
- Transcriptomic profiles were analyzed to identify cell-type-specific and conserved responses to infection.
Main Results:
- Mesenchymal cells returned to baseline transcriptomes after infection resolution.
- All mesenchymal cell types exhibited altered transcriptomes during pneumonia, indicating both conserved and distinct responses.
- Fibroblasts, particularly alveolar fibroblasts, showed significant and specific gene expression changes, highlighting their immune roles.
Conclusions:
- Lung mesenchymal cells display specialized immune activities during respiratory infections.
- Alveolar and adventitial fibroblasts exhibit differential responses, with alveolar fibroblasts being more responsive.
- These findings reveal the complex and varied contributions of mesenchymal cells to lung immunity during infection.
