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  • 1
    ISSN: 1432-1831
    Keywords: Key wordsTrypanosoma cruzi ; Interferon-γ ; Interleukin-4 ; T cell-mediated immunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interferon-γ (IFN-γ) is the most important mediator of inhibition of intracellular replication of Trypanosoma cruzi in vitro and has a protective effect against this parasite if administered in vivo. Here we have analyzed the importance of IFN-γ for resistance against a lethal infection with T. cruzi in a mouse model system. Resistant B6D2 mice survived the infection with a virulent strain of T. cruzi, whereas susceptible BALB/c mice died within 3 weeks. Both strains produced large amounts of IFN-γ after infection. Surprisingly, susceptible mice had higher serum concentrations of IFN-γ and showed, using in situ hybridization a stronger increase in IFN-γ mRNA-producing cells in their spleens than resistant mice. Moreover, this pattern was also found when immune spleen cells were stimulated with parasite antigens in vitro. However, a marked difference between these mice was found in the production of IL-4, which was much higher in susceptible mice in vivo and in vitro. No difference was found for IL-10. These data show that, at least in the mouse strain/parasite combination used, production of IFN-γ is not the decisive factor determining resistance or susceptibility to T. cruzi. Rather, it is possible that the balance between protective (e.g., IFN-γ) and exacerbative cytokines (e.g., IL-4) may decide over disease control or progression.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Medical microbiology and immunology 185 (1996), S. 189-193 
    ISSN: 1432-1831
    Keywords: Key wordsTrypanosoma cruzi ; Interleukin-12 ; Macrophages
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cytokines produced after infection with Trypanosoma cruzi have been shown to be crucial in the de-termination of resistance or susceptibility. Interferon-γ (IFN-γ) is the predominant cytokine produced after infection and has been shown to protect susceptible mice from infection. IFN-γ production by natural killer cells and T cells is induced by interleukin-12 (IL-12). Therefore, the aim of our study was to analyze the ability of T. cruzi to induce IL-12 production. Spleen cells and bone marrow-derived macrophages incubated with T. cruzi trypomastigotes induced high amounts of IL-12p40 mRNA as shown by reverse transcriptase-polymerase chain reaction. Lipopolysaccharide (LPS) was less efficient in inducing IL-12p40-specific mRNA. Furthermore, biologically active IL-12, detected by the capacity of the supernatant of infected macrophages to induce IFN-γ production in spleen cells, was produced at very high levels. In comparison, macrophages stimulated with LPS secreted drastically less IL-12. Interestingly, only live, UV- or gamma-irradiated trypanosomes, but not heat-killed parasites or lysates, were functional in this respect. In a kinetic study, in the supernatant obtained from cultures of infected macrophages, IL-12 was already detectable at 2 h after infection, peaked at 32 h and declined after 45 h.
    Type of Medium: Electronic Resource
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