Related Experiment Video
Updated: Mar 19, 2026
Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs
Published on: October 31, 2025
Single-cell landscape of piglet lung response with Actinobacillus pleuropneumoniae
Junhui Zhu1,2, Sibo Zhu3, Changyou Xia4
1State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China.
Insights
Actinobacillus pleuropneumoniae infection causes pulmonary fibrosis in pigs by altering immune cells and promoting fibroblast activity. This study reveals key mechanisms for developing targeted treatments for bacterial pneumonia and fibrotic lung diseases.
Area of Science:
- Veterinary Immunology
- Pulmonary Pathology
- Single-cell Genomics
Background:
- Pulmonary fibrosis is a fatal lung disease.
- Actinobacillus pleuropneumoniae (A. pleuropneumoniae) infection causes significant pulmonary fibrosis in pigs.
- The immune response and fibrotic mechanisms in pig lungs during A. pleuropneumoniae infection are not well understood.
Purpose of the Study:
- To investigate the immune response and cellular changes in pig lungs following A. pleuropneumoniae infection using single-cell RNA sequencing.
- To identify the specific cell types and molecular pathways involved in bacterial pneumonia-induced pulmonary fibrosis.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of piglet lungs with and without A. pleuropneumoniae infection.
- Analysis of 18 distinct cell subpopulations and their phenotypes.
- Cell-to-cell communication analysis to understand molecular interactions.
Main Results:
- A. pleuropneumoniae infection enriched monocytes, neutrophils, and plasmacytoid dendritic cells (pDCs), increasing inflammatory gene expression.
- The pathogen reduced macrophage numbers by inhibiting differentiation and inducing apoptosis.
- Pathological fibroblast-like cells increased, contributing to fibrosis, while epithelial cells decreased and underwent epithelial-mesenchymal transition.
- Enhanced interactions were observed between epithelial, vascular endothelial, pDCs, and fibroblast subsets.
Conclusions:
- This study elucidates key pathogenic mechanisms of bacterial pneumonia-induced pulmonary fibrosis in pigs.
- Findings provide a molecular resource for developing targeted strategies against A. pleuropneumoniae infection.
- The research offers insights into mechanisms relevant to human fibrotic lung disorders.
Abstract:
Pulmonary fibrosis is a prevalent, chronic, and fatal illness that poses considerable risks to life and health. Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is an archetypal bacteria responsible for inducing significant pulmonary fibrosis, resulting in substantial economic losses in the pig industry. Nevertheless, the immune response in pig lungs against this pathogen and the specific characteristics of fibrosis remain obscure. In this study, single-cell RNA sequencing (scRNA-seq) analysis of piglet lungs with or without A. pleuropneumoniae infection identified 18 subpopulations with different phenotypes. Monocytes, neutrophils, and plasmacytoid dendritic cells (pDCs) were enriched in the lungs post-infection and responded to infection by boosting IFN-γ-inducible and inflammatory-related gene expression. A. pleuropneumoniae reduces the number of macrophages by inhibiting monocyte differentiation into interstitial macrophages (IM) and alveolar macrophages (AM) and triggering AM endogenous apoptosis. Furthermore, we identified significantly augmented pathological fibroblast-like cells that contributed to the rapid development of pulmonary fibrosis. In contrast, epithelial cells were significantly decreased and included those with features of epithelial-mesenchymal transition differentiated into fibroblasts through the signaling of TGFB1 and HIF1A. Cell-to-cell communication analysis further indicated that the interaction between the epithelial, vascular endothelial, pDCs, and fibroblast subsets, except for COL3A1 fibroblasts, was enhanced mainly via CD74/(COPA or MIF) receptor ligands after infection. Our findings elucidate the key pathogenic mechanisms driving bacterial pneumonia, while establishing a comprehensive molecular resource for developing targeted strategies against A. pleuropneumoniae infection and related human fibrotic lung disorders.
