Toxoplasma gondii inhibits gamma interferon (IFN-γ)-and IFN-β-induced host cell STAT1 transcriptional activity by increasing the association of STAT1 with DNA

Emily E. Rosowski, Quynh P. Nguyen, Ana Camejo, Eric Spooner, Jeroen Saeij

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The gamma interferon (IFN-γ) response, mediated by the STAT1 transcription factor, is crucial for host defense against the intracellular pathogen Toxoplasma gondii, but prior infection with Toxoplasma can inhibit this response. Recently, it was reported that the Toxoplasma type II NTE strain prevents the recruitment of chromatin remodeling complexes containing Brahma-related gene 1 (BRG-1) to promoters of IFN-γ-induced secondary response genes such as Ciita and major histocompatibility complex class II genes in murine macrophages, thereby inhibiting their expression. We report here that a type I strain of Toxoplasma inhibits the expression of primary IFN-γ response genes such as IRF1 through a distinct mechanism not dependent on the activity of histone deacetylases. Instead, infection with a type I, II, or III strain of Toxoplasma inhibits the dissociation of STAT1 from DNA, preventing its recycling and further rounds of STAT1-mediated transcriptional activation. This leads to increased IFN-γ-induced binding of STAT1 at the IRF1 promoter in host cells and increased global IFN-γ-induced association of STAT1 with chromatin. Toxoplasma type I infection also inhibits IFN-β-induced interferon-stimulated gene factor 3-mediated gene expression, and this inhibition is also linked to increased association of STAT1 with chromatin. The secretion of proteins into the host cell by a type I strain of Toxoplasma without complete parasite invasion is not sufficient to block STAT1-mediated expression, suggesting that the effector protein responsible for this inhibition is not derived from the rhoptries

Original languageEnglish (US)
Pages (from-to)706-719
Number of pages14
JournalInfection and Immunity
Volume82
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

Fingerprint

Toxoplasma
Interferons
Interferon-gamma
DNA
Chromatin
Interferon-Stimulated Gene Factor 3
STAT1 Transcription Factor
Genes
MHC Class II Genes
Histone Deacetylases
Chromatin Assembly and Disassembly
Toxoplasmosis
Recycling
Infection
Major Histocompatibility Complex
Transcriptional Activation
Parasites
Proteins
Macrophages
Gene Expression

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Toxoplasma gondii inhibits gamma interferon (IFN-γ)-and IFN-β-induced host cell STAT1 transcriptional activity by increasing the association of STAT1 with DNA. / Rosowski, Emily E.; Nguyen, Quynh P.; Camejo, Ana; Spooner, Eric; Saeij, Jeroen.

In: Infection and Immunity, Vol. 82, No. 2, 02.2014, p. 706-719.

Research output: Contribution to journalArticle

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