Increased susceptibility of Stat4-deficient and enhanced resistance in Stat6-deficient mice to infection with Trypanosoma cruzi

Although Th1-type responses tend to be associated with resistance to Trypanosoma cruzi infection, mixed Thl and Th2 cytokine responses are generally observed in both resistant and susceptible mice, To help clarify the role of type 1 and type 2 cytokine responses in immunity to T. cruzi, mice with induced deficiencies in the Stat4 or Stat6 genes were infected with T, cruzi. As expected, Stat4(-/-) mice deficient in type 1 cytokine responses were highly susceptible to infection, exhibiting: increased parasitemia levels relative to wild-type mice and 100% mortality. In contrast, parasitemia levels find survival in Stat6-deficient mice were not different from wild type, The type 1 and type 2 cytokine bias of Stat6- and Stat4-deficient mice, respectively, was confirmed by in situ immunocytochemical analysis of cytokine-producing cells in the tissues of infected mice and by subclass analysis of anti-T. cruzi serum Abs, Notably, both Stat4- and Stat6-deficient mice produced substantial amounts of anti-T, cruzi Abs, Tissues from chronically infected Stat6-deficient mice had little to no evidence of inflammation in the heart and skeletal muscle in contrast to wild-type mice, which exhibited substantial inflammation, In situ PCR analysis of these tissues provided evidence of the persistence of T, cruzi in wild-type mice, but no evidence of parasite persistence in Stat6-deficient mice. These data suggest that type 1 T cells are required for the development of immune control to T, cruzi, but that type 2 T cells contribute to parasite persistence and increased severity of disease.