1. Microbiology and Infectious Disease
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Over-expression screen of interferon-stimulated genes identifies RARRES3 as a restrictor of Toxoplasma gondii infection

  1. Nicholas Rinkenberger
  2. Michael E Abrams
  3. Sumit K Matta
  4. John W Schoggins
  5. Neal M Alto
  6. L David Sibley  Is a corresponding author
  1. Washington University in St. Louis, United States
  2. The University of Texas Southwestern Medical Center, United States
  3. University of Texas Southwestern Medical Center, United States
Research Article
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Cite this article as: eLife 2021;10:e73137 doi: 10.7554/eLife.73137

Abstract

Toxoplasma gondii is an important human pathogen infecting an estimated 1 in 3 people worldwide. The cytokine interferon gamma (IFNγ) is induced during infection and is critical for restricting T. gondii growth in human cells. Growth restriction is presumed to be due to the induction interferon stimulated genes (ISGs) that are upregulated to protect the host from infection. Although there are hundreds of ISGs induced by IFNγ, their individual roles in restricting parasite growth in human cells remain somewhat elusive. To address this deficiency, we screened a library of 414 IFNγ induced ISGs to identify factors that impact T. gondii infection in human cells. In addition to IRF1, which likely acts through induction of numerous downstream genes, we identified RARRES3 as a single factor that restricts T. gondii infection by inducing premature egress of the parasite in multiple human cell lines. Overall, while we successfully identified a novel IFNγ induced factor restricting T. gondii infection, the limited number of ISGs capable of restricting T. gondii infection when individually expressed suggests that IFNγ mediated immunity to T. gondii infection is a complex, multifactorial process.

Data availability

RNASeq data generated here have been deposited to GEO with the accession number GSE181861.

The following data sets were generated

Article and author information

Author details

  1. Nicholas Rinkenberger

    Department of Molecular Microbiology, Washington University in St. Louis, St Louis, United States
    Competing interests
    No competing interests declared.
  2. Michael E Abrams

    Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.
  3. Sumit K Matta

    Department of Molecular Microbiology, Washington University in St. Louis, St Louis, United States
    Competing interests
    No competing interests declared.
  4. John W Schoggins

    Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    John W Schoggins, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7944-6800
  5. Neal M Alto

    Microbiology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7602-3853
  6. L David Sibley

    Department of Molecular Microbiology, Washington University in St. Louis, St Louis, United States
    For correspondence
    sibley@wustl.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7110-0285

Funding

National Institutes of Health (AI154048)

  • L David Sibley

National Institutes of Health (AI118426)

  • L David Sibley

National Institutes of Health (AI083359)

  • Neal M Alto

Welch Foundation (I-1704)

  • Neal M Alto

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

Reviewing Editor

  1. Russell E Vance, University of California, Berkeley, United States

Publication history

  1. Received: August 17, 2021
  2. Preprint posted: September 5, 2021 (view preprint)
  3. Accepted: December 5, 2021
  4. Accepted Manuscript published: December 6, 2021 (version 1)

Copyright

© 2021, Rinkenberger 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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