2. Academic Validation
  3. Macrophage peroxisomes guide alveolar regeneration and limit SARS-CoV-2 tissue sequelae

Macrophage peroxisomes guide alveolar regeneration and limit SARS-CoV-2 tissue sequelae

  • Science. 2025 Mar 7;387(6738):eadq2509. doi: 10.1126/science.adq2509.
Xiaoqin Wei 1 2,  Wei Qian 1 2,  Harish Narasimhan 1 2 3,  Ting Chan 1 2,  Xue Liu 4 5,  Mohd Arish 1 2,  Samuel Young 1 2 3,  Chaofan Li 1 2,  In Su Cheon 1 2,  Qing Yu 1 2,  Gislane Almeida-Santos 1 2,  Xiao-Yu Zhao 1 3,  Eric V Yeatts 1 2,  Olivia J Spear 1 2,  Megan Yi 1 2,  Tanyalak Parimon 4,  Yinshan Fang 6,  Young S Hahn 1 3,  Timothy N J Bullock 1 7,  Lindsay A Somerville 8,  Mark H Kaplan 9,  Anne I Sperling 8,  Yun Michael Shim 8,  Robert Vassallo 10,  Peter Chen 4 5,  Sarah E Ewald 1 3,  Anja C Roden 11,  Jianwen Que 6,  Dianhua Jiang 4 5,  Jie Sun 1 2 3
Affiliations

Affiliations

  • 1 Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA, USA.
  • 2 Division of Infectious Disease and International Health, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
  • 3 Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA, USA.
  • 4 Women's Guild Lung Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • 5 Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • 6 Columbia Center for Human Development, Department of Medicine, Columbia University Medical Center, New York, NY, USA.
  • 7 Department of Pathology, University of Virginia, Charlottesville, VA, USA.
  • 8 Division of Pulmonary Medicine and Critical Care Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
  • 9 Department of Microbiology and Immunology, Indiana University of School of Medicine, Indianapolis, IN, USA.
  • 10 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
  • 11 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
PMID: 40048515 DOI: 10.1126/science.adq2509
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.

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