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Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia.
Yang, Hu-Qin; Sun, Han; Li, Kang; Shao, Ming-Ming; Zhai, Kan; Tong, Zhao-Hui.
Afiliación
  • Yang HQ; Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, NO. 8, Gong Ti South Road, Chao yang District, Beijing, 100020, China.
  • Sun H; Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, NO. 8, Gong Ti South Road, Chao yang District, Beijing, 100020, China.
  • Li K; Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, NO. 8, Gong Ti South Road, Chao yang District, Beijing, 100020, China.
  • Shao MM; Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, NO. 8, Gong Ti South Road, Chao yang District, Beijing, 100020, China.
  • Zhai K; Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, NO. 8, Gong Ti South Road, Chao yang District, Beijing, 100020, China. zhaikan@ccmu.edu.cn.
  • Tong ZH; Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, NO. 8, Gong Ti South Road, Chao yang District, Beijing, 100020, China. tongzhaohuicy@sina.com.
Respir Res ; 25(1): 72, 2024 Feb 05.
Article en En | MEDLINE | ID: mdl-38317180
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía por Pneumocystis / Glicoproteínas de Membrana / Receptores Inmunológicos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Respir Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía por Pneumocystis / Glicoproteínas de Membrana / Receptores Inmunológicos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Respir Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido