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

Summary

This mechanistic study shows macrophage peroxisomes as regulators of inflammation resolution and alveolar regeneration during severe respiratory viral infection. Peroxisome integrity supports lipid metabolism, mitochondrial health, and restrains inflammasome/IL-1β, thereby limiting pathological alveolar transitional cell accumulation after SARS-CoV-2.

Key Findings

• Excess interferon signaling remodels and depletes macrophage peroxisomes during severe respiratory viral infection.
• Peroxisomes modulate lipid metabolism and mitochondrial health in a macrophage-type–specific manner to support alveolar repair.
• Peroxisomes restrain inflammasome activation and IL-1β release, limiting accumulation of KRT8+ alveolar transitional cells after SARS-CoV-2.

Clinical Implications

Modulating peroxisome biogenesis/function (e.g., via PPAR agonists or peroxisome proliferators) could become a strategy to promote alveolar repair after severe viral pneumonia and mitigate long-COVID lung sequelae. It also cautions against interventions that exacerbate interferon-driven peroxisome loss.

Limitations

• Predominantly preclinical models; human causal evidence is indirect
• Abstract does not report sample sizes or code/data availability

Future Directions

Test peroxisome-targeted interventions (e.g., PPAR agonists, lipid remodeling strategies) in translational/clinical studies for ARDS and post-viral lung disease; map peroxisome dynamics in human macrophages during acute infection and recovery.