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

Chen, Judy
; 
Deng, Jane C.
; 
Zemans, Rachel L.
; ; ; 
Zhang, Min
; 
Peters-Golden, Marc
; 
Goldstein, Daniel R.
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Genre
Journal article
Date
2022-11-09
Advisor
Committee member
Group
Center for Inflammation and Lung Research (Temple University)
Department
Thoracic Medicine and Surgery
Microbiology, Immunology, and Inflammation
Subject
Ageing
 Infection
 Influenza virus
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http://hdl.handle.net/20.500.12613/8232
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DOI
https://doi.org/10.1038/s41467-022-34593-y
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 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.
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Citation
Chen, J., Deng, J.C., Zemans, R.L. et al. Age-induced prostaglandin E2 impairs mitochondrial fitness and increases mortality to influenza infection. Nat Commun 13, 6759 (2022). https://doi.org/10.1038/s41467-022-34593-y
Citation to related work
Nature Research
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Nature Communications, Vol. 13
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