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De Fen Shen, Dawn M. Matteson, Nadine Tuaillon, Brandon K. Suedekum, Ronald R. Buggage, Chi-Chao Chan; Involvement of Apoptosis and Interferon-γ in Murine Toxoplasmosis. Invest. Ophthalmol. Vis. Sci. 2001;42(9):2031-2036.
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purpose. A murine toxoplasmosis model has been developed that results in central
nervous system (CNS) and ocular inflammation characterized by
encephalitis with numerous brain tissue cysts and milder inflammation
with rare tissue cysts in the eye after 4 weeks of Toxoplasma
gondii infection. In this model IFNγ and inducible nitric
oxide (iNO) are protective against T. gondii infection.
In this study, the role of apoptosis in the pathogenesis of
toxoplasmosis was investigated.
methods. C57BL/6 (wild-type mice), B6MRL/lpr, and
B6MRL/gld (defective Fas or FasL expression,
respectively) mice were infected intraperitoneally with 20 to 30 tissue
cysts of the ME-49 strain of T. gondii. Mice were killed
at days 0, 14, or 28 after infection. The eyes and brains were
harvested for histologic, immunohistochemical, and molecular studies.
Analysis included immunostaining for Fas, FasL, Bcl-2, and Bax; in situ
apoptosis detection (TUNEL assay); RT-PCR amplification for IFNγ; and
measurement of ocular nitrite levels. The control mice were
naïve mice of each strain that received no inoculation or
results. Wild-type mice appeared to constitutively express apoptotic molecules
at higher levels in the eye than in the brain. Consequently, during T. gondii infection, apoptosis was greater in the eyes
than in the brain. Untreated naïve lpr and gld mice showed no expression of Fas and FasL,
respectively. After infection, a slightly higher number of tissue cysts
(lpr, 11.8 ± 2.4; gld, 10.3 ±
3.4) were found in the brains of the mutants than in the control
animals (8.8 ± 2.9). However, no significant differences between
the number of apoptotic cells, inflammatory scores, or number of tissue
cysts were noted in the eyes. IFNγ mRNA in control mice was detected
at day 28 after infection, whereas in both mutants, mRNA production
occurred earlier, at day 14. Ocular nitrite levels were higher in lpr and gld mice than in wild-type mice.
conclusions. No significant difference in the degree of ocular inflammation and
apoptosis was detected between the wild-type and Fas or FasL mutant
mice. However, there was an earlier and subjectively greater expression
of IFNγ in the brain and eye and a higher level of nitrite in the
ocular tissue of mutant strains than in the wild type. Multiple factors
are likely to be involved in the pathogenesis of ocular
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