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Single-Cell Transcriptomics Reveals Distinct Cell Response between Acute and Chronic Pulmonary Infection of Pseudomonas Aeruginosa
67 Pages Posted: 20 Jun 2022
More...Abstract
Background: Knowledge of the changes in the immune microenvironment during pulmonary bacterial acute and chronic infections is limited. The dissection of immune systems may provide a basis for effective therapeutic strategies against bacterial infection.
Methods: Using single-cell transcriptomics, mIHC and flow cytometry, we revealed large-scale comprehensive changes in immune cell composition and high variation in cell–cell interactions after acute and chronic Pseudomonas aeruginosa infection.
Findings: Bacterial infection reprograms the genetic architecture of immune cell populations. We identified specific immune cell types, including Cxcl2+ B cells and interstitial macrophages, in response to acute and chronic infection, such as their proportions, distribution, and functional status. The distinct molecular signatures highlight the importance of the highly dynamic cell–cell interaction process in different pathological conditions, which has not been completely revealed previously.
Interpretation: These findings provide a comprehensive and unbiased immune cellular landscape for respiratory pathogenesis in mice, enabling further understanding of immunologic mechanisms in infection and inflammatory diseases.
Funding Information: This work was supported by the National Natural Science Foundation of China (No. 81922042, 82072999 and 82172285), the National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (No. Z2018B02), the Excellent Young Scientist Foundation of Sichuan University (No. 2017SCU04A16), the Innovative Spark Foundation of Sichuan University (No. 2018SCUH0032), the National Major Scientific and Technological Special Project for “Significant New Drugs Development” (No. 2018ZX09201018-013) and the 1·3·5 project of excellent development of discipline of West China Hospital of Sichuan University (No. ZYYC21001).
Declaration of Interests: The authors declare that they have no competing interests.
Ethics Approval Statement: Eight-week-old female C57BL/6 mice were purchased from Dossy Experimental Animals Company and housed in a specific-pathogen-free facility at the State Key Laboratory of Biotherapy, Sichuan University. All animal experiments were reviewed and approved by the Ethics Committee of the State Key Laboratory of Biotherapy, West China Hospital, Sichuan University (No. 20140104) and carried out in compliance with institutional guidelines concerning animal use and care of Sichuan University.
Keywords: Pseudomonas aeruginosa, pulmonary infection, single-cell RNA sequencing
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