Induction of tumor necrosis factor-α and inducible nitric oxide synthase fails to prevent toxoplasmic encephalitis in the absence of interferon-γ in genetically resistant BALB/c mice

Yasuhiro Suzuki, Hoil Kang, Stephen Parmley, Samantha Lim, Daniel Park

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Following infection with Toxoplasma gondii, certain strains of mice, such as BALB/c, are genetically resistant to development of toxoplasmic encephalitis (TE) and establish a latent chronic infection as do humans. Thus, these animals appear to be a suitable model to analyze the mechanism of resistance to TE. Since the mechanism for their genetic resistance is unknown, we examined the role of interferon-γ (IFN-γ) tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) in the resistance using BALB/c-background IFN-γ-deficient (IFN-γ(-/-)) mice. IFN- γ(-/-) and control mice were infected with the ME49 strain of T. gondii and treated with sulfadiazine to establish chronic infection. After discontinuing sulfadiazine, the IFN-γ(-/-) mice all died, whereas the control mice all survived. Histological studies revealed remarkable inflammatory changes associated with large numbers of tachyzoites in brains of the IFN-γ(-/-) mice but not in the control mice after discontinuation of sulfadiazine. Large amounts of mRNA for tachyzoite-specific SAG1 were detected in brains of only the IFN-γ(-/-) mice. IFN-γ mRNA was detected in brains of only the control mice, whereas mRNA for TNF-α and iNOS were detected in brains of both strains of mice. The amounts of the mRNA for TNFα and iNOS did not differ between these mice. Treatment of IFN-γ(-/-) mice with recombinant IFN-γ prevented development of TE. These results demonstrate that IFN-γ is crucial for genetic resistance of BALB/c mice against TE and that TNF-α and iNOS are insufficient to prevent TE in the absence of IFN-γ. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

Original languageEnglish
Pages (from-to)455-462
Number of pages8
JournalMicrobes and Infection
Volume2
Issue number5
DOIs
StatePublished - Apr 2000

Bibliographical note

Funding Information:
We thank Dr. Jack S. Remington for his support and review of the manuscript and Pauline Chu for excellent technical assistance with histological studies. This work was supported by U. S. Public Health Service grants AI04717, AI38260 and AI35956.

Keywords

  • Brain
  • Interferon-gamma
  • Nitric oxide
  • Toxoplasma
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

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