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 KRT8 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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/science.adq2509 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Glucose uptake is essential for growth in the extracellular space of the murine placenta.
Infect Immun
March 2025
Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, California, USA.
infects the placenta of its natural bovine host, which results in abortion and transmission of infection to other cattle and to humans. While the metabolism of during chronic infection of the mononuclear phagocyte system has been studied, the nutrients fueling growth of in the placenta are unknown. We found that in mice, glucose is an important carbon source for in the placenta.
View Article and Find Full Text PDFTherapeutic potential of elafibranor in alcohol-associated liver disease: Insights into macrophage modulation and fibrosis reduction.
World J Biol Chem
March 2025
Department of Biological Sciences and Chemistry, College of Arts and Sciences, University of Nizwa, Nizwa 616, Ad Dākhilīyah, Oman.
Alcohol-associated liver disease (ALD) is a major global health concern, contributing to liver injury, morbidity, and mortality. Elafibranor (EFN), a dual peroxisome proliferator-activated receptor α/δ agonist, has shown promise as a therapeutic candidate in preclinical studies. EFN reduces liver fibrosis by inhibiting lipid accumulation, apoptosis, and inflammatory pathways (LPS/TLR4/NF-κB), while enhancing autophagy and antioxidant responses.
View Article and Find Full Text PDFEndogenous ERMAP Affects T-Cell Function in EAE Mice.
Immunology
March 2025
Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University, Guiyang, Guizhou, China.
Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disease (AID) mediated by myelin-reactive CD4 T cells. Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of human MS. Erythrocyte membrane-associated protein (ERMAP) is a novel erythrocyte-specific adhesion/receptor molecule associated with erythrocyte adhesion.
View Article and Find Full Text PDFLung inflammation drives Long Covid.
Science
March 2025
Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Peroxisome dysfunction in macrophages impairs lung repair after COVID-19 in mice.
View Article and Find Full Text PDFMacrophage peroxisomes guide alveolar regeneration and limit SARS-CoV-2 tissue sequelae.
Science
March 2025
Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA, USA.
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.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!