IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-12055-2.html
   My bibliography  Save this article

Extracellular nicotinate phosphoribosyltransferase binds Toll like receptor 4 and mediates inflammation

Author

Listed:
  • Antonella Managò

    (University of Turin)

  • Valentina Audrito

    (University of Turin)

  • Francesca Mazzola

    (Polytechnic University of Marche)

  • Leonardo Sorci

    (Polytechnic University of Marche)

  • Federica Gaudino

    (University of Turin)

  • Katiuscia Gizzi

    (Italian Institute for Genomic Medicine)

  • Nicoletta Vitale

    (University of Turin)

  • Danny Incarnato

    (University of Groningen)

  • Gabriele Minazzato

    (Polytechnic University of Marche)

  • Alice Ianniello

    (Azienda Ospedaliero-Universitaria Città della Salute e della Scienza)

  • Antonio Varriale

    (Institute of Food Science, CNR)

  • Sabato D’Auria

    (Institute of Food Science, CNR)

  • Giulio Mengozzi

    (Azienda Ospedaliero-Universitaria Città della Salute e della Scienza)

  • Gianfranco Politano

    (Polytechnic University of Turin)

  • Salvatore Oliviero

    (Italian Institute for Genomic Medicine
    University of Turin)

  • Nadia Raffaelli

    (Polytechnic University of Marche)

  • Silvia Deaglio

    (University of Turin)

Abstract

Damage-associated molecular patterns (DAMPs) are molecules that can be actively or passively released by injured tissues and that activate the immune system. Here we show that nicotinate phosphoribosyltransferase (NAPRT), detected by antibody-mediated assays and mass spectrometry, is an extracellular ligand for Toll-like receptor 4 (TLR4) and a critical mediator of inflammation, acting as a DAMP. Exposure of human and mouse macrophages to NAPRT activates the inflammasome and NF-κB for secretion of inflammatory cytokines. Furthermore, NAPRT enhances monocyte differentiation into macrophages by inducing macrophage colony-stimulating factor. These NAPRT-induced effects are independent of NAD-biosynthetic activity, but rely on NAPRT binding to TLR4. In line with our finding that NAPRT mediates endotoxin tolerance in vitro and in vivo, sera from patients with sepsis contain the highest levels of NAPRT, compared to patients with other chronic inflammatory conditions. Together, these data identify NAPRT as a endogenous ligand for TLR4 and a mediator of inflammation.

Suggested Citation

  • Antonella Managò & Valentina Audrito & Francesca Mazzola & Leonardo Sorci & Federica Gaudino & Katiuscia Gizzi & Nicoletta Vitale & Danny Incarnato & Gabriele Minazzato & Alice Ianniello & Antonio Var, 2019. "Extracellular nicotinate phosphoribosyltransferase binds Toll like receptor 4 and mediates inflammation," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12055-2
    DOI: 10.1038/s41467-019-12055-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-12055-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-12055-2?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
    ---><---

    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:10:y:2019:i:1:d:10.1038_s41467-019-12055-2. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.