IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-018-08156-z.html
   My bibliography  Save this article

ATP released by intestinal bacteria limits the generation of protective IgA against enteropathogens

Author

Listed:
  • Michele Proietti

    (Università della Svizzera Italiana
    Universitätsklinikum Freiburg)

  • Lisa Perruzza

    (Università della Svizzera Italiana)

  • Daniela Scribano

    (University ‘‘Gabriele D’Annunzio’’, Via dei Vestini, Campus Universitario
    University ‘‘La Sapienza’’ of Rome, Piazzale Aldo Moro 5)

  • Giovanni Pellegrini

    (University of Zurich)

  • Rocco D’Antuono

    (Università della Svizzera Italiana)

  • Francesco Strati

    (Università della Svizzera Italiana)

  • Marco Raffaelli

    (Università della Svizzera Italiana)

  • Santiago F. Gonzalez

    (Università della Svizzera Italiana)

  • Marcus Thelen

    (Università della Svizzera Italiana)

  • Wolf-Dietrich Hardt

    (Institute of Microbiology, ETH Zürich)

  • Emma Slack

    (Institute of Microbiology, ETH Zürich)

  • Mauro Nicoletti

    (University ‘‘Gabriele D’Annunzio’’, Via dei Vestini, Campus Universitario)

  • Fabio Grassi

    (Università della Svizzera Italiana
    Istituto Nazionale Genetica Molecolare ‘‘Romeo ed Enrica Invernizzi’’
    Università degli Studi di Milano, Via Vanvitelli 32)

Abstract

T cell dependent secretory IgA (SIgA) generated in the Peyer’s patches (PPs) of the small intestine shapes a broadly diverse microbiota that is crucial for host physiology. The mutualistic co-evolution of host and microbes led to the relative tolerance of host’s immune system towards commensal microorganisms. The ATP-gated ionotropic P2X7 receptor limits T follicular helper (Tfh) cells expansion and germinal center (GC) reaction in the PPs. Here we show that transient depletion of intestinal ATP can dramatically improve high-affinity IgA response against both live and inactivated oral vaccines. Ectopic expression of Shigella flexneri periplasmic ATP-diphosphohydrolase (apyrase) abolishes ATP release by bacteria and improves the specific IgA response against live oral vaccines. Antibody responses primed in the absence of intestinal extracellular ATP (eATP) also provide superior protection from enteropathogenic infection. Thus, modulation of eATP in the small intestine can affect high-affinity IgA response against gut colonizing bacteria.

Suggested Citation

  • Michele Proietti & Lisa Perruzza & Daniela Scribano & Giovanni Pellegrini & Rocco D’Antuono & Francesco Strati & Marco Raffaelli & Santiago F. Gonzalez & Marcus Thelen & Wolf-Dietrich Hardt & Emma Sla, 2019. "ATP released by intestinal bacteria limits the generation of protective IgA against enteropathogens," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08156-z
    DOI: 10.1038/s41467-018-08156-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-08156-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-08156-z?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_s41467-018-08156-z. 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.