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 Trypan osoma cruzi infection, mixed Thl and Th2 cytokine responses are generally o bserved 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 in duced deficiencies in the Stat4 or Stat6 genes were infected with T, cruzi. As expected, Stat4(-/-) mice deficient in type 1 cytokine responses were h ighly susceptible to infection, exhibiting: increased parasitemia levels re lative to wild-type mice and 100% mortality. In contrast, parasitemia level s 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, res pectively, was confirmed by in situ immunocytochemical analysis of cytokine -producing cells in the tissues of infected mice and by subclass analysis o f anti-T. cruzi serum Abs, Notably, both Stat4- and Stat6-deficient mice pr oduced substantial amounts of anti-T, cruzi Abs, Tissues from chronically i nfected Stat6-deficient mice had little to no evidence of inflammation in t he heart and skeletal muscle in contrast to wild-type mice, which exhibited substantial inflammation, In situ PCR analysis of these tissues provided e vidence of the persistence of T, cruzi in wild-type mice, but no evidence o f parasite persistence in Stat6-deficient mice. These data suggest that typ e 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 s everity of disease.