TY - JOUR
T1 - Age-induced prostaglandin E2 impairs mitochondrial fitness and increases mortality to influenza infection
AU - Chen, Judy
AU - Deng, Jane C.
AU - Zemans, Rachel L.
AU - Bahmed, Karim
AU - Kosmider, Beata
AU - Zhang, Min
AU - Peters-Golden, Marc
AU - Goldstein, Daniel R.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85141508220&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-34593-y
DO - 10.1038/s41467-022-34593-y
M3 - Article
C2 - 36351902
AN - SCOPUS:85141508220
SN - 2041-1723
VL - 13
SP - 6759
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6759
ER -
