Abstract
The process of reactivation of latent infection with Toxoplasma gondii in immunosuppressed hosts is yet not fully understood. In the past, a number of murine models of reactivation in immunocompromised mice have been described using sulfadiazine to establish latent infection before withdrawal and subsequent reactivation. We studied the process of reactivation in brains of mice with a targeted mutation in the interferon-regulatory factor (IRF)-8 gene after withdrawal of sulfadiazine therapy. IRF-8−/− mice were orally infected with five cysts of the ME 49 strain of T. gondii. To allow establishment of latent infection with cyst formation, mice were treated with sulfadiazine starting either 3, 5, 6, or 7 days postinfection. Sulfadiazine was withdrawn after 14–21 days to allow reactivation. We observed that timing of sulfadiazine therapy had a marked impact on the course of infection and reactivation. Mice treated late after infection (days 5–7) showed increased mortality and decreased time to death compared to mice treated early after infection (group A). In the blood of mice with late (days 5–7) but not early (day 3) initiation of treatment, T. gondii-specific deoxyribonucleic acid was detected by polymerase chain reaction. Using double staining with stage-specific antibodies, tachyzoites were detectable in brains of mice with late initiation of sulfadiazine treatment but rarely within cysts thus indicating continued invasion of parasites across the blood–brain barrier. Intracerebral cyst rupture or bradyzoite–tachyzoite conversion was not detectable in IRF-8−/− mice when sulfadiazine therapy was initiated late after infection. These results indicate that continued invasion of tachyzoites rather than reactivation of latent cerebral infection impacts the course of infection in this model of reactivated toxoplasmosis. In conclusion, the timing of sulfadiazine therapy is of utmost importance for the course of infection in immunocompromised mice.
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Acknowledgments
We greatly acknowledge the expert technical assistance of Andrea Maletz and Ildiko R. Dunay. The monoclonal antibody CC2 is a gift from Uwe Gross. This work was in part supported by a grant from the Deutsche Forschungsgemeinschaft, FG463, Projekt 7A to O.L.
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Jost, C., Reiter-Owona, I. & Liesenfeld, O. The timing of sulfadiazine therapy impacts the reactivation of latent Toxoplasma infection in IRF-8−/− mice. Parasitol Res 101, 1603–1609 (2007). https://doi.org/10.1007/s00436-007-0700-y
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DOI: https://doi.org/10.1007/s00436-007-0700-y