Related Experiment Video
Updated: Apr 20, 2026
Assessing Anti-fungal Activity of Isolated Alveolar Macrophages by Confocal Microscopy
Published on: July 9, 2014
Myeloid-derived suppressor cells impair alveolar macrophages through PD-1 receptor ligation during Pneumocystis
Guang-Sheng Lei1, Chen Zhang1, Chao-Hung Lee2
1Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Abstract:
Myeloid-derived suppressor cells (MDSCs) were recently found to accumulate in the lungs during Pneumocystis pneumonia (PcP). Adoptive transfer of these cells caused lung damage in recipient mice, suggesting that MDSC accumulation is a mechanism of pathogenesis in PcP. In this study, the phagocytic activity of alveolar macrophages (AMs) was found to decrease by 40% when they were incubated with MDSCs from Pneumocystis-infected mice compared to those incubated with Gr-1(+) cells from the bone marrow of uninfected mice. The expression of the PU.1 gene in AMs incubated with MDSCs also was decreased. This PU.1 downregulation was due mainly to decreased histone 3 acetylation and increased DNA methylation caused by MDSCs. MDSCs were found to express high levels of PD-L1, and alveolar macrophages (AMs) were found to express high levels of PD-1 during PcP. Furthermore, PD-1 expression in AMs from uninfected mice was increased by 18-fold when they were incubated with MDSCs compared to those incubated with Gr-1(+) cells from the bone marrow of uninfected mice. The adverse effects of MDSCs on AMs were diminished when the MDSCs were pretreated with anti-PD-L1 antibody, suggesting that MDSCs disable AMs through PD-1/PD-L1 ligation during PcP.
Insights
Myeloid-derived suppressor cells (MDSCs) impair lung immune cells during Pneumocystis pneumonia (PcP). These cells reduce alveolar macrophage phagocytosis and function via PD-1/PD-L1 signaling, contributing to lung damage in PcP.
Area of Science:
- Immunology
- Cell Biology
- Pulmonary Medicine
Background:
- Myeloid-derived suppressor cells (MDSCs) accumulate in the lungs during Pneumocystis pneumonia (PcP).
- MDSC accumulation is implicated in PcP pathogenesis and lung damage.
Purpose of the Study:
- To investigate the mechanism by which MDSCs affect alveolar macrophages (AMs) during PcP.
- To determine the role of PD-1/PD-L1 interaction in MDSC-mediated AM dysfunction.
Main Methods:
- Incubation of AMs with MDSCs from PcP-infected mice or control cells.
- Assessment of AM phagocytic activity and PU.1 gene expression.
- Analysis of histone 3 acetylation and DNA methylation.
- Evaluation of PD-1 and PD-L1 expression.
- Treatment of MDSCs with anti-PD-L1 antibody.
Main Results:
- MDSCs significantly decreased AM phagocytic activity by 40% and reduced PU.1 gene expression.
- PU.1 downregulation was linked to decreased histone 3 acetylation and increased DNA methylation induced by MDSCs.
- MDSCs expressed high PD-L1, and AMs expressed high PD-1 during PcP.
- MDSC incubation increased AM PD-1 expression 18-fold.
- Anti-PD-L1 antibody treatment diminished the adverse effects of MDSCs on AMs.
Conclusions:
- MDSCs impair AM phagocytic function and gene expression during PcP.
- MDSC-mediated AM dysfunction is primarily driven by PD-1/PD-L1 ligation.
- Targeting the PD-1/PD-L1 pathway may mitigate MDSC-induced lung pathology in PcP.
More Related Videos
Related Concept Videos
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Inflammation
01:29Pneumonia II: Pathophysiology