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Updated: May 24, 2025
Author Spotlight: Studying Macrophage-Epithelial Cell Interactions in Salivary Gland Regeneration After Injury
Published on: November 17, 2023
Macrophage peroxisomes guide alveolar regeneration and limit SARS-CoV-2 tissue sequelae
Xiaoqin Wei1,2, Wei Qian1,2, Harish Narasimhan1,2,3
1Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA, USA.
Abstract:
Peroxisomes are vital but often overlooked metabolic organelles. We found that excessive interferon signaling remodeled macrophage peroxisomes. This loss of peroxisomes impaired inflammation resolution and lung repair during severe respiratory viral infections. Peroxisomes were found to modulate lipid metabolism and mitochondrial health in a macrophage type-specific manner and enhanced alveolar macrophage-mediated tissue repair and alveolar regeneration after viral infection. Peroxisomes also prevented excessive macrophage inflammasome activation and IL-1β release, limiting accumulation of KRT8high dysplastic epithelial progenitors following viral injury. Pharmacologically enhancing peroxisome biogenesis mitigated both acute symptoms and post-acute sequelae of COVID-19 (PASC) in animal models. Thus, macrophage peroxisome dysfunction contributes to chronic lung pathology and fibrosis after severe acute respiratory syndrome coronavirus 2 infection.
Insights
Excessive interferon signaling damages macrophage peroxisomes, impairing lung repair after viral infections. Enhancing peroxisome function may treat lung injury and COVID-19 sequelae.
Area of Science:
- Cell Biology
- Immunology
- Respiratory Medicine
Background:
- Peroxisomes are essential organelles involved in various metabolic processes.
- Their role in immune cells, particularly macrophages, during viral infections is not well understood.
- Dysfunctional peroxisomes may contribute to chronic lung diseases.
Purpose of the Study:
- To investigate the impact of interferon signaling on macrophage peroxisomes during viral infections.
- To determine the role of peroxisomes in inflammation resolution, lung repair, and COVID-19 pathogenesis.
- To explore pharmacological strategies for enhancing peroxisome function to treat lung injury.
Main Methods:
- Studied macrophage peroxisome remodeling induced by excessive interferon signaling in viral infection models.
- Assessed the effects of peroxisome loss on inflammation resolution, lung repair, and macrophage function.
- Utilized animal models to evaluate the therapeutic potential of enhancing peroxisome biogenesis for acute symptoms and post-acute sequelae of COVID-19 (PASC).
Main Results:
- Excessive interferon signaling led to macrophage peroxisome remodeling and loss, impairing inflammation resolution and lung repair.
- Peroxisomes modulate macrophage lipid metabolism and mitochondrial health, promoting alveolar macrophage-mediated tissue repair.
- Enhancing peroxisome biogenesis pharmacologically ameliorated acute viral symptoms and PASC in animal models, preventing excessive inflammasome activation and IL-1β release.
Conclusions:
- Macrophage peroxisome dysfunction contributes to chronic lung pathology and fibrosis after severe acute respiratory syndrome coronavirus 2 infection.
- Peroxisome enhancement represents a potential therapeutic strategy for viral-induced lung injury and associated chronic conditions.
- Targeting macrophage peroxisomes offers a novel approach to mitigate severe respiratory viral infection consequences and PASC.
