Age-elevated prostaglandin E2enhances mortality to influenza infection

Summary Aging impairs the immune responses to influenza A virus (IAV), resulting in increased mortality to IAV infections in older adults. With aging, there is reduced number and impaired function of alveolar macrophages (AMs), cells critical for defense against IAV. However, factors within the aged lung that impair AMs are not fully known. Using a murine model of IAV infection, we observed that aging increased the level of prostaglandin E 2 (PGE 2 ) in the bronchoalveolar lavage fluid (BALF) of aged mice compared to young mice. Blockade of the PGE 2 receptor EP2 in aged mice increased AM numbers and subsequently enhanced survival to IAV. Additionally, PGE 2 impaired the mitochondrial health of AMs. We also identified senescent type II alveolar epithelial cells (AECs) as a source of the aged-associated PGE 2 in the lung. Our results reveal a crosstalk between AECs and AMs, via PGE 2 , that compromises host defense to IAV infection with aging.