STAT1 is essential for antimicrobial effector function but dispensable for gamma interferon production during Toxoplasma gondii infection

Infect Immun. 2004 Mar;72(3):1257-64. doi: 10.1128/IAI.72.3.1257-1264.2004.


The opportunistic protozoan Toxoplasma gondii is a prototypic Th1-inducing pathogen inducing strong gamma interferon (IFN-gamma) cytokine responses that are required to survive infection. Intracellular signaling intermediate STAT1 mediates many effects of IFN-gamma and is implicated in activation of T-bet, a master regulator of Th1 differentiation. Here, we show that T. gondii-infected STAT1-null mice fail to upregulate the IFN-gamma-dependent effector molecules inducible nitric oxide synthase (iNOS), IGTP, and LRG-47, which are required for mice to survive infection. Both T-bet and interleukin-12 receptor beta2 (IL-12Rbeta2) failed to undergo normal upregulation in response to T. gondii. Development of IFN-gamma-producing CD4(+) and CD8(+) T lymphocytes was severely curtailed in the absence of STAT1, but a substantial level of STAT1-independent non-T-cell-derived IFN-gamma was induced. Absence of STAT1 also resulted in increased IL-4, Arg1, Ym1, and Fizz1, markers of Th2 differentiation and alternative macrophage activation. Together, the results show that T. gondii induces STAT1-dependent T-lymphocyte and STAT1-independent non-T-cell IFN-gamma production, but that effector functions of this type 1 cytokine cannot operate in the absence of STAT1, resulting in extreme susceptibility to acute infection.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cytokines / biosynthesis
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • GTP Phosphohydrolases / biosynthesis
  • GTP-Binding Proteins / biosynthesis
  • Immunity, Innate
  • Interferon-gamma / biosynthesis*
  • Macrophages / immunology
  • Mice
  • Mice, Knockout
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase Type II
  • STAT1 Transcription Factor
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • Toxoplasmosis, Animal / etiology*
  • Toxoplasmosis, Animal / immunology
  • Toxoplasmosis, Animal / physiopathology
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / physiology*


  • Cytokines
  • DNA, Complementary
  • DNA-Binding Proteins
  • Ifi1 protein, mouse
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Trans-Activators
  • Interferon-gamma
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Igtp protein, mouse