Age-elevated prostaglandin E2 enhances mortality to influenza infection

Abstract

SummaryAging 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 E2 (PGE2) in the bronchoalveolar lavage fluid (BALF) of aged mice compared to young mice. Blockade of the PGE2 receptor EP2 in aged mice increased AM numbers and subsequently enhanced survival to IAV. Additionally, PGE2 impaired the mitochondrial health of AMs. We also identified senescent type II alveolar epithelial cells (AECs) as a source of the aged-associated PGE2 in the lung. Our results reveal a crosstalk between AECs and AMs, via PGE2, that compromises host defense to IAV infection with aging.