Resistance to Trypanosoma cruzi infection in mice does not necessarily correlate with production of interferon-g in vivo

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.