1. Neonatal imprinting of alveolar macrophages via neutrophil-derived 12-HETE
- Author
-
Pernet, Erwan, Sun, Sarah, Sarden, Nicole, Gona, Saideep, Nguyen, Angela, Khan, Nargis, Mawhinney, Martin, Tran, Kim A., Chronopoulos, Julia, Amberkar, Dnyandeo, Sadeghi, Mina, Grant, Alexandre, Wali, Shradha, Prevel, Renaud, Ding, Jun, Martin, James G., Thanabalasuriar, Ajitha, Yipp, Bryan G., Barreiro, Luis B., and Divangahi, Maziar
- Abstract
Resident-tissue macrophages (RTMs) arise from embryonic precursors1,2, yet the developmental signals that shape their longevity remain largely unknown. Here we demonstrate in mice genetically deficient in 12-lipoxygenase and 15-lipoxygenase (Alox15−/−mice) that neonatal neutrophil-derived 12-HETE is required for self-renewal and maintenance of alveolar macrophages (AMs) during lung development. Although the seeding and differentiation of AM progenitors remained intact, the absence of 12-HETE led to a significant reduction in AMs in adult lungs and enhanced senescence owing to increased prostaglandin E2production. A compromised AM compartment resulted in increased susceptibility to acute lung injury induced by lipopolysaccharide and to pulmonary infections with influenza A virus or SARS-CoV-2. Our results highlight the complexity of prenatal RTM programming and reveal their dependency on in transeicosanoid production by neutrophils for lifelong self-renewal.
- Published
- 2023
- Full Text
- View/download PDF