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Proc Natl Acad Sci U S A. 2019 Aug 27;116(35):17480-17491. doi: 10.1073/pnas.1904637116. Epub 2019 Aug 14.

Toxoplasma gondii effector TgIST blocks type I interferon signaling to promote infection.

Author information

1
Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63130.
2
Department of Internal Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63130.
3
Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63130; sibley@wustl.edu.

Abstract

In contrast to the importance of type II interferon-γ (IFN-γ) in control of toxoplasmosis, the role of type I IFN is less clear. We demonstrate here that TgIST, a secreted effector previously implicated in blocking type II IFN-γ signaling, also blocked IFN-β responses by inhibiting STAT1/STAT2-mediated transcription in infected cells. Consistent with a role for type I IFN in cell intrinsic control, ∆Tgist mutants were more susceptible to growth inhibition by murine and human macrophages activated with IFN-β. Additionally, type I IFN was important for production of IFN-γ by natural killer (NK) cells and recruitment of inflammatory monocytes at the site of infection. Mice lacking type I IFN receptors (Ifnar1-/-) showed increased mortality following infection with wild-type parasites and decreased virulence of ∆Tgist parasites was restored in Ifnar1-/- mice. The findings highlight the importance of type I IFN in control of toxoplasmosis and illuminate a parasite mechanism to counteract the effects of both type I and II IFN-mediated host defenses.

KEYWORDS:

NK cell; central nervous system; inflammatory monocyte; interferon; transcriptome

PMID:
31413201
PMCID:
PMC6717281
[Available on 2020-02-14]
DOI:
10.1073/pnas.1904637116

Conflict of interest statement

The authors declare no conflict of interest.

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