tetano
Editor, Senior Moderator
Science
. 2025 Mar 7;387(6738):eadq2509.
doi: 10.1126/science.adq2509. Epub 2025 Mar 7. Macrophage peroxisomes guide alveolar regeneration and limit SARS-CoV-2 tissue sequelae
Xiaoqin Wei[SUP] 1 2 [/SUP], Wei Qian[SUP] 1 2 [/SUP], Harish Narasimhan[SUP] 1 2 3 [/SUP], Ting Chan[SUP] 1 2 [/SUP], Xue Liu[SUP] 4 5 [/SUP], Mohd Arish[SUP] 1 2 [/SUP], Samuel Young[SUP] 1 2 3 [/SUP], Chaofan Li[SUP] 1 2 [/SUP], In Su Cheon[SUP] 1 2 [/SUP], Qing Yu[SUP] 1 2 [/SUP], Gislane Almeida-Santos[SUP] 1 2 [/SUP], Xiao-Yu Zhao[SUP] 1 3 [/SUP], Eric V Yeatts[SUP] 1 2 [/SUP], Olivia J Spear[SUP] 1 2 [/SUP], Megan Yi[SUP] 1 2 [/SUP], Tanyalak Parimon[SUP] 4 [/SUP], Yinshan Fang[SUP] 6 [/SUP], Young S Hahn[SUP] 1 3 [/SUP], Timothy N J Bullock[SUP] 1 7 [/SUP], Lindsay A Somerville[SUP] 8 [/SUP], Mark H Kaplan[SUP] 9 [/SUP], Anne I Sperling[SUP] 8 [/SUP], Yun Michael Shim[SUP] 8 [/SUP], Robert Vassallo[SUP] 10 [/SUP], Peter Chen[SUP] 4 5 [/SUP], Sarah E Ewald[SUP] 1 3 [/SUP], Anja C Roden[SUP] 11 [/SUP], Jianwen Que[SUP] 6 [/SUP], Dianhua Jiang[SUP] 4 5 [/SUP], Jie Sun[SUP] 1 2 3 [/SUP]
Affiliations
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[SUP]high[/SUP] 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.
. 2025 Mar 7;387(6738):eadq2509.
doi: 10.1126/science.adq2509. Epub 2025 Mar 7. Macrophage peroxisomes guide alveolar regeneration and limit SARS-CoV-2 tissue sequelae
Xiaoqin Wei[SUP] 1 2 [/SUP], Wei Qian[SUP] 1 2 [/SUP], Harish Narasimhan[SUP] 1 2 3 [/SUP], Ting Chan[SUP] 1 2 [/SUP], Xue Liu[SUP] 4 5 [/SUP], Mohd Arish[SUP] 1 2 [/SUP], Samuel Young[SUP] 1 2 3 [/SUP], Chaofan Li[SUP] 1 2 [/SUP], In Su Cheon[SUP] 1 2 [/SUP], Qing Yu[SUP] 1 2 [/SUP], Gislane Almeida-Santos[SUP] 1 2 [/SUP], Xiao-Yu Zhao[SUP] 1 3 [/SUP], Eric V Yeatts[SUP] 1 2 [/SUP], Olivia J Spear[SUP] 1 2 [/SUP], Megan Yi[SUP] 1 2 [/SUP], Tanyalak Parimon[SUP] 4 [/SUP], Yinshan Fang[SUP] 6 [/SUP], Young S Hahn[SUP] 1 3 [/SUP], Timothy N J Bullock[SUP] 1 7 [/SUP], Lindsay A Somerville[SUP] 8 [/SUP], Mark H Kaplan[SUP] 9 [/SUP], Anne I Sperling[SUP] 8 [/SUP], Yun Michael Shim[SUP] 8 [/SUP], Robert Vassallo[SUP] 10 [/SUP], Peter Chen[SUP] 4 5 [/SUP], Sarah E Ewald[SUP] 1 3 [/SUP], Anja C Roden[SUP] 11 [/SUP], Jianwen Que[SUP] 6 [/SUP], Dianhua Jiang[SUP] 4 5 [/SUP], Jie Sun[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 40048515
- DOI: 10.1126/science.adq2509
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[SUP]high[/SUP] 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.