RESUMEN
Infection with a myotropic Trypanosoma cruzi clone induces maternal fertility failure. In the current work, we evaluated whether reduction of maternal parasitaemia before mating has beneficial effects on pregnancy outcome. Female mice were subjected to benznidazole (Bz) treatment after infection. On day 30 of therapy, mating was assessed and pregnancy outcome was determined on day 14 of gestation. Fetal resorptions diminished in T. cruzi-infected Bz-treated mice compared with T. cruzi-infected untreated mice. This was in agreement with the reduction in the blood/solid tissue parasite load and with the percentage of necrotic foci in placental samples from T. cruzi-infected Bz-treated females. To study eventual changes in the immune homeostasis of T. cruzi-infected Bz-treated mice, activation of the immune system was evaluated at the end of Bz therapy and before mating. We found specific IgG1 reduction resulting in a predominance of specific IgG2a, reduced numbers of CD69+ CD4+ cells and diminished frequency and numbers of CD44+ T cells. Concanavalin A-stimulated splenocytes from T. cruzi-infected Bz-treated mice produced higher amounts of IFN-gamma than T. cruzi-infected untreated mice. These results indicate that reduction of maternal parasite load improves pregnancy outcome. These findings correlate with a favourable modulation of the immune response.
Asunto(s)
Enfermedad de Chagas/parasitología , Parasitemia/parasitología , Complicaciones Parasitarias del Embarazo/parasitología , Trypanosoma cruzi/fisiología , Animales , Anticuerpos Antiprotozoarios/sangre , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Linfocitos T CD4-Positivos/inmunología , Enfermedad de Chagas/tratamiento farmacológico , Femenino , Regulación de la Expresión Génica , Receptores de Hialuranos/metabolismo , Inmunoglobulina G/sangre , Interferón gamma/metabolismo , Lectinas Tipo C , Ratones , Nitroimidazoles/uso terapéutico , Parasitemia/tratamiento farmacológico , Placenta/parasitología , Embarazo , Complicaciones Parasitarias del Embarazo/tratamiento farmacológico , Resultado del Embarazo , Bazo/citología , Bazo/metabolismo , Factores de TiempoRESUMEN
There is agreement today about the role that the characteristics of the population of Trypanosoma cruzi play in the pathogenesis of the different clinical forms of Chagas disease. In our laboratory, we have studied the outcome of the infection of mice with two populations with polar biological behaviour: RA and CA-I. We have demonstrated that the neuromuscular damage is, in part, mediated by different T cell subsets. We have also observed that the T cell phenotype responsible for the pathology and the targetted tissues depend on the parasite population. Although we found no differences regarding the reactivity of IgG to native nerve structures in sera from mice infected with either strain, it is presumed that the humoral response would play an additional role in the development of strain-dependent neuromuscular pathology since passive transfer of sera from mice infected with RA triggered alterations of the nerve action potential whereas sera from CA-I-infected mice did not. We have also detected a reduction in the fertility of female mice infected with CA-I/K98, whereas females infected with RA showed no difference in comparison with uninfected controls. However, congenital transmission was only observed in mice infected with RA. The differences observed in fertility, in newborn survival, and in the number of fetal resorptions in mice infected with the myotropic strain could be attributed to the uterine inflammatory response, since no estrous alterations were observed between infected and control groups.
Asunto(s)
Enfermedad de Chagas/parasitología , Enfermedades Neuromusculares/parasitología , Linfocitos T/inmunología , Trypanosoma cruzi/clasificación , Animales , Antígenos de Protozoos/inmunología , Enfermedad de Chagas/inmunología , Femenino , Subgrupos Linfocitarios/inmunología , Ratones , Embarazo , Especificidad de la Especie , Trypanosoma cruzi/inmunologíaRESUMEN
We assessed the performance of an enzyme-linked immunosorbent assay (ELISA) with the Trypanosoma cruzi epimastigote ribosomal fraction (Tulahuen and Y strains) in order to improve the diagnostic specificity of the test. A total of 100 serum samples from patients with chronic Chagas' disease from Brazil and Argentina were studied. Sera from 116 patients, without Chagas' disease, including 10 with active mucocutaneous leishmaniasis and 20 with visceral leishmaniasis, were used as controls. Immunoglobulin G (IgG) antibodies against the ribosomal fraction (ribonucleoproteins [RNPs]) in the ELISA were found in 97% of samples from patients with Chagas' disease. A total of 99% of the sera from patients without the disease were negative, including sera from patients with mucocutaneous and visceral leishmaniases. The distribution of IgG isotypes in randomly chosen serum samples was determined by ELISA; IgG1 and IgG3 were predominant (100% exhibited IgG1 and 85% exhibited IgG3, and 50% also presented the IgG2 isotype. The distribution of the IgG subclasses was confirmed by the Western blot (immunoblot) technique. When total IgG was assayed by Western blot assay, no correlation was found between the pattern of serum reactivity and the clinical features of the patients with Chagas' disease. Therefore, no typical profile of polypeptide recognition could be associated with any clinical form of Chagas' disease (cardiomyopathy or megaviscera). Our results showed that sera from patients with Chagas' disease react with ribosomal antigens and display a typical profile of IgG isotypes (IgG1 plus IgG3). The RNP ELISA seems to have improved specificity compared with those of routine techniques such as the indirect immunofluorescence assay and hemagglutination because it better discriminates between patients with Chagas' disease and patients without the disease. Since sera from patients with leishmaniasis failed to show cross-reactivity with this antigen, the ELISA seems useful for detecting Chagas' disease as well as confirming the nature of sera, when it is doubtful whether the patients has Chagas' disease, by the isotype distribution of IgG.
Asunto(s)
Antígenos de Protozoos , Enfermedad de Chagas/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Ribonucleoproteínas/inmunología , Trypanosoma cruzi/inmunología , Animales , Anticuerpos Antiprotozoarios/sangre , Western Blotting , Enfermedad de Chagas/inmunología , Reacciones Cruzadas , Ensayo de Inmunoadsorción Enzimática/estadística & datos numéricos , Estudios de Evaluación como Asunto , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Sensibilidad y EspecificidadRESUMEN
PGE2 involvement in experimental Trypanosoma cruzi infection depends on the lethal capacity of the parasite subpopulation used. Mice acutely infected with non-lethal K98 displayed an enhancement in PGE2 serum levels during the acute period, while those infected with lethal T. cruzi subpopulations (RA or K98-2) showed levels not different from normal mice. The enhancement detected in K98 group could be related both to an increased number of CD8+ T cell number and to enhanced PGE2 release per cell by CD8+; values of PGE2 release by adherent cells were not altered in this group. Treatment with cyclooxygenase inhibitors enhanced mortality rates of mice infected with K98, and administration of 16,16-dimethyl PGE2 (dPGE) reversed this effect. However, mice infected with RA did not reduce their mortality rates by administration of diverse doses of dPGE. These findings suggest that PGE2 could play a role in resistance in mice infected with K98.