Defining Inflammatory Cell States in Acute and Chronic Pulmonary Infection with Pseudomonas aeruginosa by Single-Cell Transcriptomics

Using mouse models of acute and chronic Pseudomonas aeruginosa (P. aeruginosa) pulmonary infection, combined with single-cell RNA sequencing (scRNA-seq), flow cytometry and fluorescent multiplex immunohistochemistry (mIHC) and other experimental strategies, we map immune changes and particular immune cell subtypes during acute and chronic infection.This integrated method profiled extensive cell atlas of healthy and infected mouse lungs and defined subpopulations of main immune cells not further subdivided before. We found that the proportions and status of several kinds of pulmonary immune cells were changed a lot after P. aeruginosa pulmonary infection.In particular, the percentage of neutrophils and CD200+ B cells increased significantly after acute infection, while interstitial macrophages (IMs) expanded distinctly during chronic infections, respectively. By analyzing public datasets, we have also found consistent findings of the changes of myeloid subpopulations in other bacterial and SARS-CoV-2 infections, thus arising a hypothesis that CD200+ B cells and IMs may play an unanticipated role in progression of infection diseases. Therefore, our findings provide novel perspectives for P. aeruginosa infection and have potential impact on the development of vaccines, antibiotics, and immunotherapeutic strategies when facing with pathogen challenges. Single-cell RNA sequencing of lung tissues from wild type, acute and chronic Pseudomonas aeruginosa (P. aeruginosa) pulmonary infected mice (n=2), combined with bulk-RNA seq. Please note that the matrix.mtx file has been updated on Mar 7, 2023.