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.
Zhu et al. (Tue,) studied this question.
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