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

Author

Listed:
  • Judy Chen

    (University of Michigan
    University of Michigan)

  • Jane C. Deng

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Rachel L. Zemans

    (University of Michigan
    University of Michigan)

  • Karim Bahmed

    (Temple University
    Temple University)

  • Beata Kosmider

    (Temple University
    Temple University)

  • Min Zhang

    (University of Michigan)

  • Marc Peters-Golden

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Daniel R. Goldstein

    (University of Michigan
    University of Michigan
    University of Michigan)

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.

Suggested Citation

  • Judy Chen & Jane C. Deng & Rachel L. Zemans & Karim Bahmed & Beata Kosmider & Min Zhang & Marc Peters-Golden & Daniel R. Goldstein, 2022. "Age-induced prostaglandin E2 impairs mitochondrial fitness and increases mortality to influenza infection," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34593-y
    DOI: 10.1038/s41467-022-34593-y
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    References listed on IDEAS

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    1. Paras S. Minhas & Amira Latif-Hernandez & Melanie R. McReynolds & Aarooran S. Durairaj & Qian Wang & Amanda Rubin & Amit U. Joshi & Joy Q. He & Esha Gauba & Ling Liu & Congcong Wang & Miles Linde & Yu, 2021. "Restoring metabolism of myeloid cells reverses cognitive decline in ageing," Nature, Nature, vol. 590(7844), pages 122-128, February.
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