Macrophage peroxisomes guide alveolar regeneration and limit post-acute sequelae of SARS-CoV-2 infection (PASC) 2101
Year: 2025
Type: article
Abstract: Description Peroxisomes are vital yet often overlooked metabolic organelles. Here we demonstrate that exuberant interferon signaling remodeled the macrophage peroxisome compartment after severe COVID-19. Lack of macrophage peroxisomes resulted in impaired inflammation resolution and defective lung repair, causing heightened acute morbidity and mortality during SARS-CoV-2 infection. Peroxisomes exhibited cell-type specific modulation of lipid metabolism, enhancing mitochondrial health critical for lung macrophage repair program and alveolar cell self-renewal. Peroxisomes also prevented excessive inflammasome activation and IL-1β release, thereby limiting the accumulation of KRT8high dysplastic epithelial progenitors and facilitating their proper differentiation into functional alveolar cells post viral injury. Dysfunction in macrophage peroxisomes contributed to chronic lung pathology and fibrosis post SARS-CoV-2 infection. Furthermore, pharmacologically enhancing peroxisome biogenesis mitigated acute symptoms and limited chronic sequelae post SARS-CoV-2 infection (PASC). Our data reveal a peroxisome-centric pro-recovery therapeutic strategy for managing both acute and chronic conditions after respiratory viral infections. Funding Sources The study was in part supported by the US National Institutes of Health grants AI147394, AG069264, AI112844, HL170961, AI176171 and AI154598 to J.S, R01HL132287, R01HL167202 and R01HL132177 to Y.M.S, F31HL170746 and T32AI007496 to H.N, R01HL155759 and R01HL159953 to P.C, P01-HL108793 to D.J, and HL159675, HL152293 and AI163753 to J.Q. Topic Categories Viral Immunology (VIR)
Source: The Journal of Immunology
Authors: Xiaoqin Wei, Jie Sun
Institution: University of Virginia
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Roles of tissue-resident helper T cells in mucosal immunity against influenzainfection, G9000016370, G9000042161, G9000057425, G9000080218, G9000116368, G9000140724, G9000155652, G9000182982, G9000267656, G9000313051, Host cellular network governing the development of post SARS-CoV-2 tissue sequelae
OpenAlex ID: W4416448992
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