1. Immunology and Inflammation
  2. Microbiology and Infectious Disease

NAIP-NLRC4-deficient mice are susceptible to shigellosis

  1. Patrick S Mitchell
  2. Justin L Roncaioli
  3. Elizabeth A Turcotte
  4. Lisa Goers
  5. Roberto A Chavez
  6. Angus Y Lee
  7. Cammie F Lesser
  8. Isabella Rauch
  9. Russell E Vance  Is a corresponding author
  1. University of California, Berkeley, United States
  2. Harvard Medical School, United States
  3. Massachusetts General Hospital, United States
  4. Oregon Health and Sciences University, United States
https://doi.org/10.7554/eLife.59022
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Cite this article
  1. Patrick S Mitchell
  2. Justin L Roncaioli
  3. Elizabeth A Turcotte
  4. Lisa Goers
  5. Roberto A Chavez
  6. Angus Y Lee
  7. Cammie F Lesser
  8. Isabella Rauch
  9. Russell E Vance
(2020)
NAIP-NLRC4-deficient mice are susceptible to shigellosis
eLife 9:e59022.
https://doi.org/10.7554/eLife.59022
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Abstract

Bacteria of the genus Shigella cause shigellosis, a severe gastrointestinal disease that is a major cause of diarrhea-associated mortality in humans. Mice are highly resistant to Shigella and the lack of a tractable physiological model of shigellosis has impeded our understanding of this important human disease. Here we propose that the differential susceptibility of mice and humans to Shigella is due to mouse-specific activation of the NAIP–NLRC4 inflammasome. We find that NAIP–NLRC4-deficient mice are highly susceptible to oral Shigella infection and recapitulate the clinical features of human shigellosis. Although inflammasomes are generally thought to promote Shigella pathogenesis, we instead demonstrate that intestinal epithelial cell (IEC)-specific NAIP–NLRC4 activity is sufficient to protect mice from shigellosis. In addition to describing a new mouse model of shigellosis, our results suggest that the lack of an inflammasome response in IECs may help explain the susceptibility of humans to shigellosis.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Patrick S Mitchell

    Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.

  2. Justin L Roncaioli

    Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.

  3. Elizabeth A Turcotte

    Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.

  4. Lisa Goers

    Department of Microbiology, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.

  5. Roberto A Chavez

    Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.

  6. Angus Y Lee

    Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.

  7. Cammie F Lesser

    Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, United States
    Competing interests
    No competing interests declared.

  8. Isabella Rauch

    Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, United States
    Competing interests
    No competing interests declared.

  9. Russell E Vance

    Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    rvance@berkeley.edu
    Competing interests
    Russell E Vance, R.E.V. has a financial relationship with Aduro BioTech and Ventus Therapeutics and both he and the companies may benefit from the commercialization of the results of this research.Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6686-3912

Funding

Howard Hughes Medical Institute

  • Russell E Vance

National Institutes of Health (AI075039,AI063302)

  • Russell E Vance

National Institutes of Health (AI064285,AI128743)

  • Cammie F Lesser

Jane Coffin Childs Memorial Fund for Medical Research (Postdoctoral Fellowship)

  • Patrick S Mitchell

Irving H. Wiesenfeld CEND Fellow (Graduate Student Fellowship)

  • Justin L Roncaioli

UC Berkeley Department of Molecular and Cell Biology, NIH (Graduate Training Grant 5T32GM007232-42)

  • Elizabeth A Turcotte

Brit d'Arbeloff MGH Research Scholar

  • Cammie F Lesser

Medical Research Foundation (MRF2012)

  • Isabella Rauch

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (AUP-2014-09-6665-1) of the University of California Berkeley.

Copyright

© 2020, Mitchell et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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