Acute and chronic experimental Trypanosoma cruzi infection in the rat. Response to systemic treatment with recombinant rat interferon-gamma.

We examined the effects of recombinant rat interferon-gamma (IFN-gamma) injections on the parasitologic, serologic, immunologic and histopathologic features of acute and chronic experimental Trypanosoma cruzi (T. cruzi) infections in "l" rats. Upon infection at weaning, two rat groups were allocated to receive a 20-day cycle of IFN-gamma injections, 20,000 IU/rat each, which started at 1, and 7 days post-infection (pi). Treatment with IFN-gamma, initiated at either 1 or 7 days pi, resulted in comparatively lower peak parasitemias (P < 0.02) but in similar levels of anti-T. cruzi circulating antibodies and serum IFN-gamma activities. The latter appeared significantly increased during acute infection whereas biologically active tumor necrosis factor was virtually undetectable in serum from infected rats regardless of whether they had been given IFN-gamma or not. The prevalence of chronic focal myocarditis in IFN-gamma-treated infected rats showed no differences with respect to the one recorded in control-infected counterparts. The inverse CD4/CD8 ratio of spleen and lymph node T cells that usually accompanies chronic infection was reversed by IFN-gamma. Mononuclear cells carrying class II I-A and I-E molecules, that were found to have increased at both compartments, appeared also modified upon IFN-gamma treatment with an overincrease of I-A-positive cells, and a normalization of I-E-bearing cells.

Infection with Trypanosoma cruzi during pregnancy in rats and a decrease in chronic myocardial lesions in their infected offspring.

To ascertain whether maternal infection with Trypanosoma cruzi may influence the course of the parasitic infection in offspring, two groups of female 1 rats were mated with syngeneic sires. One group of females was infected with 10(6) trypomastigotes of T. cruzi three times at weekly intervals. All offspring were nursed by their mothers until weaning and then separated into two groups of young, one to be infected with the same dose of T. cruzi, and the other to remain uninfected. Infection of pregnant rats caused no aggravated disease but resulted in a self-controlled infection that did not cause any deaths or affect their reproductive capacity. The number of young delivered, litter size, fertility coefficient, and offspring weights at weaning were also unaffected by maternal infection; however, the survival coefficient decreased in comparison with values recorded in the offspring of uninfected mothers. The latter finding is likely due to neonatal transmission, since bloodstream forms of T. cruzi were observed in a few offspring of infected mothers. While infected offspring whose mothers had been inoculated with T. cruzi during pregnancy were not protected from acute infection, the occurrence of chronic focal myocarditis was less prevalent when compared with that recorded in chronically infected offspring born to uninfected mothers.

Enhanced myocardial lesions in chronically Trypanosoma cruzi-infected rats subjected to adult thymectomy.

Control animals and rats infected 90 days earlier, by inoculation of 1 x 10(6) trypomastigotes of Trypanosoma cruzi at weaning, were subjected to adult thymectomy (ATx) or sham operation (S-ATx) and assessed 3 months later for the presence of myocardial lesions and levels of lymph node and spleen T-cell populations. Chronic focal myocarditis (CFM) developed in 78% and 84% of S-ATx or ATx infected rats, respectively. While the two groups of infected rats did not differ as to the occurrence of myocardial lesions, large foci of CFM were more prevalent in ATx infected rats. Chronic T. cruzi (Tc) infection resulted in decreased CD4+ and increased CD8+ lymph node and spleen cell, with CD8+ lymphocytes being lowered to normal values in the spleen of the ATx infected group. It is suggested that ATx might act by interfering with a down-regulating immunoregulatory mechanism, leading to an exacerbation of autoimmune reactions believed to be involved in the generation of myocardial damage.