Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia
Abstract Background Pneumocystis pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%. However, current understanding of the variation in host immune response against Pneumocystis across different timepo...
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| 格式: | 文件 |
| 语言: | English |
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BMC
2024-02-01
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| 丛编: | Respiratory Research |
| 主题: | |
| 在线阅读: | https://doi.org/10.1186/s12931-024-02709-1 |
| _version_ | 1827326438354714624 |
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| author | Hu-Qin Yang Han Sun Kang Li Ming-Ming Shao Kan Zhai Zhao-Hui Tong |
| author_facet | Hu-Qin Yang Han Sun Kang Li Ming-Ming Shao Kan Zhai Zhao-Hui Tong |
| author_sort | Hu-Qin Yang |
| collection | DOAJ |
| description | Abstract Background Pneumocystis pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%. However, current understanding of the variation in host immune response against Pneumocystis across different timepoints is limited. Methods In this study, we conducted a time-resolved single-cell RNA sequencing analysis of CD45+ cells sorted from lung tissues of mice infected with Pneumocystis. The dynamically changes of the number, transcriptome and interaction of multiply immune cell subsets in the process of Pneumocystis pneumonia were identified according to bioinformatic analysis. Then, the accumulation of Trem2hi interstitial macrophages after Pneumocystis infection was verified by flow cytometry and immunofluorescence. We also investigate the role of Trem2 in resolving the Pneumocystis infection by depletion of Trem2 in mouse models. Results Our results characterized the CD45+ cell composition of lung in mice infected with Pneumocystis from 0 to 5 weeks, which revealed a dramatic reconstitution of myeloid compartments and an emergence of PCP-associated macrophage (PAM) following Pneumocystis infection. PAM was marked by the high expression of Trem2. We also predicted that PAMs were differentiated from Ly6C+ monocytes and interacted with effector CD4+ T cell subsets via multiple ligand and receptor pairs. Furthermore, we determine the surface markers of PAMs and validated the presence and expansion of Trem2hi interstitial macrophages in PCP by flow cytometry. PAMs secreted abundant pro-inflammation cytokines, including IL-6, TNF-α, GM-CSF, and IP-10. Moreover, PAMs inhibited the proliferation of T cells, and depletion of Trem2 in mouse lead to reduced fungal burden and decreased lung injury in PCP. Conclusion Our study delineated the dynamic transcriptional changes in immune cells and suggests a role for PAMs in PCP, providing a framework for further investigation into PCP’s cellular and molecular basis, which could provide a resource for further discovery of novel therapeutic targets. |
| first_indexed | 2024-03-07T14:44:30Z |
| format | Article |
| id | doaj.art-407b292291be45bba3b4cd085c7bf0a1 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-07T14:44:30Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-407b292291be45bba3b4cd085c7bf0a12024-03-05T20:02:35ZengBMCRespiratory Research1465-993X2024-02-0125111410.1186/s12931-024-02709-1Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumoniaHu-Qin Yang0Han Sun1Kang Li2Ming-Ming Shao3Kan Zhai4Zhao-Hui Tong5Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical UniversityDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical UniversityAbstract Background Pneumocystis pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%. However, current understanding of the variation in host immune response against Pneumocystis across different timepoints is limited. Methods In this study, we conducted a time-resolved single-cell RNA sequencing analysis of CD45+ cells sorted from lung tissues of mice infected with Pneumocystis. The dynamically changes of the number, transcriptome and interaction of multiply immune cell subsets in the process of Pneumocystis pneumonia were identified according to bioinformatic analysis. Then, the accumulation of Trem2hi interstitial macrophages after Pneumocystis infection was verified by flow cytometry and immunofluorescence. We also investigate the role of Trem2 in resolving the Pneumocystis infection by depletion of Trem2 in mouse models. Results Our results characterized the CD45+ cell composition of lung in mice infected with Pneumocystis from 0 to 5 weeks, which revealed a dramatic reconstitution of myeloid compartments and an emergence of PCP-associated macrophage (PAM) following Pneumocystis infection. PAM was marked by the high expression of Trem2. We also predicted that PAMs were differentiated from Ly6C+ monocytes and interacted with effector CD4+ T cell subsets via multiple ligand and receptor pairs. Furthermore, we determine the surface markers of PAMs and validated the presence and expansion of Trem2hi interstitial macrophages in PCP by flow cytometry. PAMs secreted abundant pro-inflammation cytokines, including IL-6, TNF-α, GM-CSF, and IP-10. Moreover, PAMs inhibited the proliferation of T cells, and depletion of Trem2 in mouse lead to reduced fungal burden and decreased lung injury in PCP. Conclusion Our study delineated the dynamic transcriptional changes in immune cells and suggests a role for PAMs in PCP, providing a framework for further investigation into PCP’s cellular and molecular basis, which could provide a resource for further discovery of novel therapeutic targets.https://doi.org/10.1186/s12931-024-02709-1Pneumocystis pneumoniaSingle-cell RNA sequencingInterstitial macrophagesTrem2 |
| spellingShingle | Hu-Qin Yang Han Sun Kang Li Ming-Ming Shao Kan Zhai Zhao-Hui Tong Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia Respiratory Research Pneumocystis pneumonia Single-cell RNA sequencing Interstitial macrophages Trem2 |
| title | Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia |
| title_full | Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia |
| title_fullStr | Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia |
| title_full_unstemmed | Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia |
| title_short | Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia |
| title_sort | dynamics of host immune responses and a potential function of trem2hi interstitial macrophages in pneumocystis pneumonia |
| topic | Pneumocystis pneumonia Single-cell RNA sequencing Interstitial macrophages Trem2 |
| url | https://doi.org/10.1186/s12931-024-02709-1 |
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