IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-10733-9.html
   My bibliography  Save this article

IL-33 drives group 2 innate lymphoid cell-mediated protection during Clostridium difficile infection

Author

Listed:
  • Alyse L. Frisbee

    (University of Virginia Health System)

  • Mahmoud M. Saleh

    (University of Virginia Health System)

  • Mary K. Young

    (University of Virginia Health System)

  • Jhansi L. Leslie

    (University of Virginia Health System)

  • Morgan E. Simpson

    (University of Virginia Health System)

  • Mayuresh M. Abhyankar

    (University of Virginia Health System)

  • Carrie A. Cowardin

    (University of Virginia Health System)

  • Jennie Z. Ma

    (University of Virginia School of Medicine)

  • Patcharin Pramoonjago

    (University of Virginia Health System)

  • Stephen D. Turner

    (University of Virginia School of Medicine)

  • Alice P. Liou

    (Seres Therapeutics)

  • Erica L. Buonomo

    (University of Virginia Health System)

  • William A. Petri

    (University of Virginia Health System
    University of Virginia Health System
    University of Virginia Health System)

Abstract

Clostridium difficile (C. difficile) incidence has tripled over the past 15 years and is attributed to the emergence of hypervirulent strains. While it is clear that C. difficile toxins cause damaging colonic inflammation, the immune mechanisms protecting from tissue damage require further investigation. Through a transcriptome analysis, we identify IL-33 as an immune target upregulated in response to hypervirulent C. difficile. We demonstrate that IL-33 prevents C. difficile-associated mortality and epithelial disruption independently of bacterial burden or toxin expression. IL-33 drives colonic group 2 innate lymphoid cell (ILC2) activation during infection and IL-33 activated ILC2s are sufficient to prevent disease. Furthermore, intestinal IL-33 expression is regulated by the microbiota as fecal microbiota transplantation (FMT) rescues antibiotic-associated depletion of IL-33. Lastly, dysregulated IL-33 signaling via the decoy receptor, sST2, predicts C. difficile-associated mortality in human patients. Thus, IL-33 signaling to ILC2s is an important mechanism of defense from C. difficile colitis.

Suggested Citation

  • Alyse L. Frisbee & Mahmoud M. Saleh & Mary K. Young & Jhansi L. Leslie & Morgan E. Simpson & Mayuresh M. Abhyankar & Carrie A. Cowardin & Jennie Z. Ma & Patcharin Pramoonjago & Stephen D. Turner & Ali, 2019. "IL-33 drives group 2 innate lymphoid cell-mediated protection during Clostridium difficile infection," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10733-9
    DOI: 10.1038/s41467-019-10733-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-10733-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-10733-9?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Laurence D. W. Luu & Abhimanu Pandey & Sudarshan Paramsothy & Chinh Ngo & Natalia Castaño-Rodríguez & Cheng Liu & Michael A. Kamm & Thomas J. Borody & Si Ming Man & Nadeem O. Kaakoush, 2024. "Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice," Nature Communications, Nature, vol. 15(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:10:y:2019:i:1:d:10.1038_s41467-019-10733-9. 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.