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

Sumit K. Matta, Philipp Olias, Zhou Huang, Qiuling Wang, Eugene Park, Wayne M. Yokoyama, L. David Sibley

Research output: Contribution to journalArticle

3 Scopus citations

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, ΔTgist 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 ΔTgist parasites was restored in Ifnar-/- 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.

Original languageEnglish
Pages (from-to)17480-17491
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number35
DOIs
StatePublished - Aug 27 2019

Keywords

  • Central nervous system
  • Inflammatory monocyte
  • Interferon
  • NK cell
  • Transcriptome

Fingerprint Dive into the research topics of 'Toxoplasma gondii effector TgIST blocks type I interferon signaling to promote infection'. Together they form a unique fingerprint.

  • Cite this