4 research outputs found

    Phosphatidylserine Exposure by Toxoplasma gondii Is Fundamental to Balance the Immune Response Granting Survival of the Parasite and of the Host

    Get PDF
    Phosphatidylserine (PS) exposure on the cell surface indicates apoptosis, but has also been related to evasion mechanisms of parasites, a concept known as apoptotic mimicry. Toxoplasma gondii mimics apoptotic cells by exposing PS, inducing secretion of TGF-beta1 by infected activated macrophages leading to degradation of inducible nitric oxide (NO) synthase, NO production inhibition and consequently persisting in these cells. Here PS+ and PS− subpopulation of tachyzoites were separated and the entrance mechanism, growth and NO inhibition in murine macrophages, and mice survival and pathology were analyzed. Infection index in resident macrophages was similar for both PS subpopulations but lower when compared to the total T. gondii population. Growth in resident macrophages was higher for the total T. gondii population, intermediate for the PS+ and lower for the PS− subpopulation. Production of NO by activated macrophages was inhibited after infection with the PS+ subpopulation and the total populations of tachyzoites. However, the PS− subpopulation was not able to inhibit NO production. PS+ subpopulation invaded macrophages by active penetration as indicated by tight-fitting vacuoles, but the PS− subpopulation entered macrophages by phagocytosis as suggested by loose-fitting vacuoles containing these tachyzoites. The entrance mechanism of both subpopulations was confirmed in a non-professional phagocytic cell line where only the PS+ tachyzoites were found inside these cells in tight-fitting vacuoles. Both subpopulations of T. gondii killed mice faster than the total population. Clear signs of inflammation and no tachyzoites were seen in the peritoneal cavity of mice infected with the PS− subpopulation. Moreover, mice infected with the PS+ subpopulation had no sign of inflammation and the parasite burden was intense. These results show that PS+ and PS− subpopulations of T. gondii are necessary for a successful toxoplasma infection indicating that both subpopulations are required to maintain the balance between inflammation and parasite growth

    Analysis of <i>Toxoplasma gondii</i> infection <i>in vivo</i>.

    No full text
    <p>C57/BL6 mice were infected with PS<sup>+</sup>, PS<sup>−</sup> subpopulations or the total population of <i>T. gondii</i>. (A) Survival curve of mice after the infection with <i>T. gondii</i>. Kaplan Meier analysis <i>p</i> = 0.0273. (B) Light microscopy of spleen and liver tissue of C57/BL6 mice after interaction with PS<sup>+</sup> or PS<sup>−</sup> subpopulation of <i>T. gondii</i>. Bars = 100 µm. (B1–3) Spleen images after interaction with the PS<sup>−</sup> (B1), PS<sup>+</sup> (B2) or the total population of <i>T. gondii</i> (B3). Note the presence of inflammatory cells in B1 (arrows) and the presence of parasites in B2 and B3 (arrows). (B4–6) Liver images after interaction with PS<sup>−</sup> (B4), PS<sup>+</sup> (B5) or the total population of <i>T. gondii</i> (B6). Note similar results obtained for the spleen tissue. Inset – Transmission electron microscopy: B2, Bar = 2 µm; B4, Bar = 16 µm. Results are from two independent experiments with 6 animals per group.</p

    Phosphatidylserine (PS)<sup>+</sup> and PS<sup>−</sup> subpopulations of <i>Toxoplasma gondii</i> were magnetically separated and analyzed by flow cytometry after annexin-V staining.

    No full text
    <p>(A) PS<sup>+</sup> subpopulation of <i>T. gondii</i>. (B) PS<sup>−</sup> subpopulation of <i>T. gondii</i>. The black lines represent control parasites without Annexin – V and the gray lines refer to the isolated subpopulations. Results from one representative experiment out of five.</p
    corecore