Age-induced prostaglandin E2 impairs mitochondrial fitness and increases mortality to influenza infection
Year: 2022
Type: article
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 E 2 (PGE 2 ), as such a factor. Senescent type II alveolar epithelial cells (AECs) are overproducers of PGE 2 within the aged lung. PGE 2 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 PGE 2 receptor EP2 in aged mice improves AM mitochondrial function, increases AM numbers and enhances survival to IAV infection. In conclusion, our study reveals a key mechanism that compromises host defense to IAV, and possibly other respiratory infections, with aging and suggests potential new therapeutic or preventative avenues to protect against viral respiratory disease in older adults.
Source: Nature Communications
Institutions: University of Michigan, Temple University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: U.S. Department of Health and Human Services, U.S. Department of Veterans Affairs, University of Michigan, Max-Planck-Gesellschaft, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, Michigan Nutrition Obesity Research Center, Medical School, University of Michigan
Awards: G1573153106, G1639961477, G1650628242, G1721348878, Research Training in Experimental Immunology, G1923858223, G2139182585, Regulation of alveolar epithelial regeneration by T cells, Interrogating the Effects of Aging on Influenza Infections: The Role of Prostaglandin E2, G2579244795, G2880120850, G3642999741, Mechanisms of dysregulated immunity with aging, G4206027271, G4496397841, G532738286, G5544006853, Alveolar epithelial cell dysfunction induced by flavored e-cigarette aerosols, G5849556715, G6121826059, G6614410681, Physician Scientist Training in Age-Related Diseases, G7474985567, G8045391961, Role of mitophagy in age-related respiratory and vascular diseases, G8957744790, Michigan Nutrition Obesity Research Center, Mechanisms of Alveolar Homeostasis, Injury, Regeneration, and Fibrosis, Novel Functions of Lung Macrophages and Fibroblasts in Pulmonary Inflammation and Fibrosis
OpenAlex ID: W4308738479