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Single-Cell Insights Into Macrophage Subtypes in Pulmonary Infections
Zhaoheng Lin1,2, Yuxiao Zheng1,2, Yu Zhong1
1Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
Abstract:
Macrophages are pivotal innate immune cells that play essential roles in pathogen recognition, inflammation modulation, and tissue repair during pulmonary infections. Macrophages have remarkable plasticity that is shaped by diverse external stimuli to adapt to the dynamic lung microenvironment. Traditional models of macrophage polarization (M1/M2) cannot capture the full complexity of macrophage heterogeneity and diverse functions during lung infections. Recent advances in single-cell omics have provided new insights into distinct macrophage subtypes, revealing their unique transcriptional profiles across various stages of infection. This review focuses on the functional plasticity of pulmonary macrophages and how environmental cues modulate their activation and effector functions. An integrative classification framework that defines six major functional macrophage subtypes in pulmonary infections, based on single-cell omics with functional perspectives is proposed. This framework refines the understanding of macrophage heterogeneity and offers a foundation for developing targeted immunotherapeutic strategies against lung infections.
Insights
Pulmonary macrophages are key immune cells in lung infections. New research proposes a framework classifying six functional macrophage subtypes, improving understanding and guiding immunotherapies for lung infections.
Area of Science:
- Immunology
- Cell Biology
- Infectious Diseases
Background:
- Macrophages are crucial innate immune cells in lung infections, involved in pathogen recognition, inflammation, and repair.
- Macrophage plasticity allows adaptation to the lung environment, but traditional M1/M2 polarization models are insufficient.
- Single-cell omics reveal complex macrophage heterogeneity and diverse functions during infection.
Purpose of the Study:
- To review the functional plasticity of pulmonary macrophages and environmental influences on their activation.
- To propose an integrative classification framework for macrophage subtypes in pulmonary infections.
- To enhance understanding of macrophage heterogeneity for targeted immunotherapies.
Main Methods:
- Review of recent advances in single-cell omics technologies.
- Analysis of transcriptional profiles of pulmonary macrophages during infection.
- Integration of functional perspectives with omics data.
Main Results:
- Traditional M1/M2 models do not fully represent macrophage diversity in lung infections.
- Distinct macrophage subtypes with unique transcriptional profiles exist across infection stages.
- An integrative classification framework identifies six major functional macrophage subtypes.
Conclusions:
- Pulmonary macrophage heterogeneity is complex and dynamic during infections.
- The proposed six-subtype framework refines understanding beyond M1/M2 polarization.
- This framework provides a basis for developing targeted immunotherapeutic strategies for lung infections.
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