Integrated multi-omics analyses reveal the altered transcriptomic characteristics of pulmonary macrophages in immunocompromised hosts with Pneumocystis pneumonia

作者：Yawen Wang, Kang Li, Weichao Zhao, Yalan Liu, Ting Li, Huqin Yang, Zhaohui Tong, Nan Song · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2023.1179094 · 被引用次数：17 · 研究领域：Pneumocystis jirovecii pneumonia detection and treatment、Pneumonia and Respiratory Infections、Macrophage Migration Inhibitory Factor

Introduction With the extensive use of immunosuppressants, immunosuppression-associated pneumonitis including Pneumocystis jirovecii pneumonia (PCP) has received increasing attention. Though aberrant adaptive immunity has been considered as a key reason for opportunistic infections, the characteristics of innate immunity in these immunocompromised hosts remain unclear. Methods In this study, wild type C57BL/6 mice or dexamethasone-treated mice were injected with or without Pneumocystis . Bronchoalveolar lavage fluids (BALFs) were harvested for the multiplex cytokine and metabolomics analysis. The single-cell RNA sequencing (scRNA-seq) of indicated lung tissues or BALFs was performed to decipher the macrophages heterogeneity. Mice lung tissues were further analyzed via quantitative polymerase chain reaction (qPCR) or immunohistochemical staining. Results We found that the secretion of both pro-inflammatory cytokines and metabolites in the Pneumocystis -infected mice are impaired by glucocorticoids. By scRNA-seq, we identified seven subpopulations of macrophages in mice lung tissues. Among them, a group of Mmp12 + macrophages is enriched in the immunocompetent mice with Pneumocystis infection. Pseudotime trajectory showed that these Mmp12 + macrophages are differentiated from Ly6c + classical monocytes, and highly express pro-inflammatory cytokines elevated in BALFs of Pneumocystis -infected mice. In vitro , we confirmed that dexamethasone impairs the expression of Lif , Il1b ,...