Age-induced prostaglandin E₂ impairs mitochondrial fitness and increases mortality to influenza infection.

ABSTRACT: Aging impairs the immune responses to influenza A virus (IAV), resulting in increased mortality to IAV infections in older adults. However, the factors within the aged lung that compromise host defense to IAV remain unknown. Using a murine model and human samples, we identified prostaglandin E₂ (PGE₂), as such a factor. Senescent type II alveolar epithelial cells (AECs) are overproducers of PGE₂ within the aged lung. PGE₂ impairs the proliferation of alveolar macrophages (AMs), critical cells for defense against respiratory pathogens, via reduction of oxidative phosphorylation and mitophagy. Importantly, blockade of the PGE₂ receptor EP2 in aged mice improves AM mitochondrial function, increases AM numbers and enhances survival to IAV

SUBMITTER: Chen J 

PROVIDER: S-EPMC9643978 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature