Induction of tumor necrosis factor-alpha and inducible nitric oxide synthase fails to prevent toxoplasmic encephalitis in the absence of interferon-gamma in genetically resistant BALB/c mice
Y. Suzuki et al., Induction of tumor necrosis factor-alpha and inducible nitric oxide synthase fails to prevent toxoplasmic encephalitis in the absence of interferon-gamma in genetically resistant BALB/c mice, MICROBES IN, 2(5), 2000, pp. 455-462
Following infection with Toxoplasma gondii, certain strains of mice, such a
s BALB/c, are genetically resistant to development of toxoplasmic encephali
tis (TE) and establish a latent chronic infection as do humans. Thus, these
animals appear to be a suitable model to analyze the mechanism of resistan
ce to TE. Since the mechanism for their genetic resistance is unknown, we e
xamined the role of interferon-gamma (IFN-gamma) tumor necrosis factor-alph
a (TNF-alpha) and inducible nitric oxide synthase (INOS) in the resistance
using BALB/c-background IFN-gamma-deficient (IFN-gamma(-/-)) mice. IFN-gamm
a(-/-) and control mice were infected with the ME49 strain of T. gondii and
treated with sulfadiazine to establish chronic infection. After discontinu
ing sulfadiazine, the IFN-gamma(-/-) mice all died, whereas the control mic
e all survived. Histological studies revealed remarkable inflammatory chang
es associated with large numbers of tachyzoites in brains of the IFN-gamma(
-/-) mice but not in the control mice after discontinuation of sulfadiazine
. Large amounts of mRNA for tachyzoite-specific SAG1 were detected in brain
s of only the IFN-gamma(-/-) mice. IFN-gamma mRNA was detected in brains of
only the control mice, whereas mRNA for TNF-alpha and INOS were detected i
n brains of both strains of mice. The amounts of the mRNA for TNF-alpha and
INOS did not differ between these mice. Treatment of IFN-gamma(-/-) mice w
ith recombinant IFN-gamma prevented development of TE. These results demons
trate that IFN-gamma is crucial for genetic resistance of BALB/c mice again
st TE and that TNF-alpha and INOS are insufficient to prevent TE in the abs
ence of IFN-gamma. (C) 2000 Editions scientifiques et medicales Elsevier SA
S.