IFN-gamma in human Chagas' disease: protection or pathology?

An apparently paradoxical role for IFN-gamma in human Chagas'disease was observed when studying the pattern of cytokine production by peripheral blood mononuclear cells (PBMC) obtained from two groups of chagasic patients after specific stimulation with Trypanosoma cruzi-derived antigens. The groups studied were 1) patients treated with bendnidazole during the acute phase of Trypanosoma cruzi infection and 2) chronically infected untreated patients. In the treated group, higher levels of IFN-gamma were produced by PBMC from individuals cured after treatment when compared to non-cured patients. In contrast, in the chronically infected group (not treated) higher levels of IFN-gamma were produced by PBMC from cardiac patients in comparison with asymptomatic (indeterminate) patients. This apparently paradoxical role for IFN-gamma in human Chagas'disease is discussed in terms of the possibility of a temporal difference in IFN-gamma production during the initial stages of the infection (acute phase) in the presence or absence of chemotherapy. The maintenance of an immune response with high levels of IFN-gamma production during the chronic phase of the infection may favor cure or influence the development of the cardiac form of the disease.

The effect of reinoculation with trypomastigotes on the level of protective antibodies in mice chronically infected with T. cruzi

1. The levels of specific antibodies were determined in sera from mice chronically infected with T. cruzi using indirect immunofluorescence, complement-mediated lysis, and neutralization of bloodstream trypomastigote (Try) infectivity upon their incubation with the test sera in vitro and passive transfer of immune sera. 2. The sera were obtained at different times after T. cruzi inoculation performed one to five times using live Y or CL bloodstream Try, two polar strains of T. cruzi. 3. Hight levels of protective and nonprotective antibodies were detected form week 4, the first interval studied, onward, regardless of number of inoculations and time of infection. 4. Sera from CL-infected mice had lower antibody titers at week 4 and the ability of whole sera or semipurified IgG to neutralize the infectivity of bloodstream Try was lower at this time. 5. All other sera obtained during the chronic phase were strongly effective in decreasing parasite infectivity as measured by lower parasitemia and mortality of mice inoculated with the serum-treated Y strain bloodstream Try