Overexpression screen of interferon-stimulated genes identifies RARRES3 as a restrictor of <i>Toxoplasma gondii</i> infection.

Abstract

<i>Toxoplasma gondii</i> is an important human pathogen infecting an estimated one in three people worldwide. The cytokine interferon gamma (IFNγ) is induced during infection and is critical for restricting <i>T. gondii</i> growth in human cells. Growth restriction is presumed to be due to the induction of 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 <i>T. gondii</i> infection in human cells. In addition to IRF1, which likely acts through the induction of numerous downstream genes, we identified RARRES3 as a single factor that restricts <i>T. gondii</i> infection by inducing premature egress of the parasite in multiple human cell lines. Overall, while we successfully identified a novel IFNγ induced factor restricting <i>T. gondii</i> infection, the limited number of ISGs capable of restricting <i>T. gondii</i> infection when individually expressed suggests that IFNγ-mediated immunity to <i>T. gondii</i> infection is a complex, multifactorial process.