IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34593-y.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34593-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-34593-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Laura K. Hamilton & Gaël Moquin-Beaudry & Chenicka L. Mangahas & Federico Pratesi & Myriam Aubin & Anne Aumont & Sandra E. Joppé & Alexandre Légiot & Annick Vachon & Mélanie Plourde & Catherine Mounie, 2022. "Stearoyl-CoA Desaturase inhibition reverses immune, synaptic and cognitive impairments in an Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Niranjana Natarajan & Jonathan Florentin & Ebin Johny & Hanxi Xiao & Scott Patrick O’Neil & Liqun Lei & Jixing Shen & Lee Ohayon & Aaron R. Johnson & Krithika Rao & Xiaoyun Li & Yanwu Zhao & Yingze Zh, 2024. "Aberrant mitochondrial DNA synthesis in macrophages exacerbates inflammation and atherosclerosis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Stefano Suzzi & Tommaso Croese & Adi Ravid & Or Gold & Abbe R. Clark & Sedi Medina & Daniel Kitsberg & Miriam Adam & Katherine A. Vernon & Eva Kohnert & Inbar Shapira & Sergey Malitsky & Maxim Itkin &, 2023. "N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Anaísa V. Ferreira & Juan Carlos Alarcon-Barrera & Jorge Domínguez-Andrés & Özlem Bulut & Gizem Kilic & Priya A. Debisarun & Rutger J. Röring & Hatice N. Özhan & Eva Terschlüsen & Athanasios Ziogas & , 2023. "Fatty acid desaturation and lipoxygenase pathways support trained immunity," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34593-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.