Over-expression screen of interferon-stimulated genes identifies RARRES3 as a restrictor of Toxoplasma gondii infection
- Washington University in St. Louis, United States
- The University of Texas Southwestern Medical Center, United States
- University of Texas Southwestern Medical Center, United States
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.
Article and author information
Author details
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
- Russell E Vance, University of California, Berkeley, United States
Version history
- Received: August 17, 2021
- Preprint posted: September 5, 2021 (view preprint)
- Accepted: December 5, 2021
- Accepted Manuscript published: December 6, 2021 (version 1)
- Version of Record published: January 25, 2022 (version 2)
- Version of Record updated: May 19, 2022 (version 3)
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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Over-expression screen of interferon-stimulated genes identifies RARRES3 as a restrictor of Toxoplasma gondii infection
eLife 10:e73137.
https://doi.org/10.7554/eLife.73137
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