IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40545-x.html
   My bibliography  Save this article

NAD(H) homeostasis underlies host protection mediated by glycolytic myeloid cells in tuberculosis

Author

Listed:
  • Hayden T. Pacl

    (University of Alabama at Birmingham)

  • Krishna C. Chinta

    (University of Alabama at Birmingham)

  • Vineel P. Reddy

    (University of Alabama at Birmingham)

  • Sajid Nadeem

    (University of Alabama at Birmingham)

  • Ritesh R. Sevalkar

    (University of Alabama at Birmingham)

  • Kievershen Nargan

    (University of KwaZulu Natal)

  • Kapongo Lumamba

    (University of KwaZulu Natal)

  • Threnesan Naidoo

    (University of KwaZulu Natal
    Walter Sisulu University)

  • Joel N. Glasgow

    (University of Alabama at Birmingham)

  • Anupam Agarwal

    (University of Alabama at Birmingham)

  • Adrie J. C. Steyn

    (University of Alabama at Birmingham
    University of KwaZulu Natal
    University of Alabama at Birmingham)

Abstract

Mycobacterium tuberculosis (Mtb) disrupts glycolytic flux in infected myeloid cells through an unclear mechanism. Flux through the glycolytic pathway in myeloid cells is inextricably linked to the availability of NAD+, which is maintained by NAD+ salvage and lactate metabolism. Using lung tissue from tuberculosis (TB) patients and myeloid deficient LDHA (LdhaLysM−/−) mice, we demonstrate that glycolysis in myeloid cells is essential for protective immunity in TB. Glycolytic myeloid cells are essential for the early recruitment of multiple classes of immune cells and IFNγ-mediated protection. We identify NAD+ depletion as central to the glycolytic inhibition caused by Mtb. Lastly, we show that the NAD+ precursor nicotinamide exerts a host-dependent, antimycobacterial effect, and that nicotinamide prophylaxis and treatment reduce Mtb lung burden in mice. These findings provide insight into how Mtb alters host metabolism through perturbation of NAD(H) homeostasis and reprogramming of glycolysis, highlighting this pathway as a potential therapeutic target.

Suggested Citation

  • Hayden T. Pacl & Krishna C. Chinta & Vineel P. Reddy & Sajid Nadeem & Ritesh R. Sevalkar & Kievershen Nargan & Kapongo Lumamba & Threnesan Naidoo & Joel N. Glasgow & Anupam Agarwal & Adrie J. C. Steyn, 2023. "NAD(H) homeostasis underlies host protection mediated by glycolytic myeloid cells in tuberculosis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40545-x
    DOI: 10.1038/s41467-023-40545-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40545-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40545-x?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. Erika M. Palmieri & Marieli Gonzalez-Cotto & Walter A. Baseler & Luke C. Davies & Bart Ghesquière & Nunziata Maio & Christopher M. Rice & Tracey A. Rouault & Teresa Cassel & Richard M. Higashi & Andre, 2020. "Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    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. Erika M. Palmieri & Ronald Holewinski & Christopher L. McGinity & Ciro L. Pierri & Nunziata Maio & Jonathan M. Weiss & Vincenzo Tragni & Katrina M. Miranda & Tracey A. Rouault & Thorkell Andresson & D, 2023. "Pyruvate dehydrogenase operates as an intramolecular nitroxyl generator during macrophage metabolic reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Guihong Lu & Xiaojun Wang & Feng Li & Shuang Wang & Jiawei Zhao & Jinyi Wang & Jing Liu & Chengliang Lyu & Peng Ye & Hui Tan & Weiping Li & Guanghui Ma & Wei Wei, 2022. "Engineered biomimetic nanoparticles achieve targeted delivery and efficient metabolism-based synergistic therapy against glioblastoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Juraj Adamik & Paul V. Munson & Deena M. Maurer & Felix J. Hartmann & Sean C. Bendall & Rafael J. Argüello & Lisa H. Butterfield, 2023. "Immuno-metabolic dendritic cell vaccine signatures associate with overall survival in vaccinated melanoma patients," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Juraj Adamik & Paul V. Munson & Felix J. Hartmann & Alexis J. Combes & Philippe Pierre & Matthew F. Krummel & Sean C. Bendall & Rafael J. Argüello & Lisa H. Butterfield, 2022. "Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells," Nature Communications, Nature, vol. 13(1), pages 1-19, 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:14:y:2023:i:1:d:10.1038_s41467-023-40545-x. 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.