Leishmania (Leishmania) chagasi-infected mice as a model for the study of glomerular lesions in visceral leishmaniasis.

Renal involvement in visceral leishmaniasis (VL) is very frequent but the pathogenesis of this nephropathy is poorly understood. In previous studies using dogs with VL we have detected new immunopathological elements in the glomeruli such as T cells and adhesion molecules. Although Leishmania (Leishmania) chagasi-infected dogs and hamsters are considered to be good models for VL, their use is limited for immunopathologic studies. The use of isogenic mouse strains susceptible to L. (L.) chagasi infection was an alternative but, on the other hand, the renal lesions of these animals have not yet been characterized. Thus, our purpose in the present study was to characterize mice infected with L. (L.) chagasi as a suitable model to study VL nephropathy. Kidney samples were obtained from control mice (N = 12) and from BALB/c mice (N = 24) injected intraperitoneally with 20 million L. (L.) chagasi amastigotes 7, 15, and 30 days after injection and processed for histopathological studies and detection of IgG deposits. Glomerular hypercellularity was clearly visible and, upon Mason's trichrome and periodic acid methenamine silver staining, a pattern suggestive of mesangial proliferative glomerulonephritis was observed in mice with VL. Time-dependent IgG deposits were also seen in infected mice. We consider L. (L.) chagasi-infected mice to be a suitable model for studies of the immunopathogenesis of glomerular lesions in VL.

Leishmania (Leishmania) chagasi-infected mice as a model for the study of glomerular lesions in visceral leishmaniasis

Renal involvement in visceral leishmaniasis (VL) is very frequent but the pathogenesis of this nephropathy is poorly understood. In previous studies using dogs with VL we have detected new immunopathological elements in the glomeruli such as T cells and adhesion molecules. Although Leishmania (Leishmania) chagasi-infected dogs and hamsters are considered to be good models for VL, their use is limited for immunopathologic studies. The use of isogenic mouse strains susceptible to L. (L.) chagasi infection was an alternative but, on the other hand, the renal lesions of these animals have not yet been characterized. Thus, our purpose in the present study was to characterize mice infected with L. (L.) chagasi as a suitable model to study VL nephropathy. Kidney samples were obtained from control mice (N = 12) and from BALB/c mice (N = 24) injected intraperitoneally with 20 million L. (L.) chagasi amastigotes 7, 15, and 30 days after injection and processed for histopathological studies and detection of IgG deposits. Glomerular hypercellularity was clearly visible and, upon Mason's trichrome and periodic acid methenamine silver staining, a pattern suggestive of mesangial proliferative glomerulonephritis was observed in mice with VL. Time-dependent IgG deposits were also seen in infected mice. We consider L. (L.) chagasi-infected mice to be a suitable model for studies of the immunopathogenesis of glomerular lesions in VL.

Cell-mediated immune response in megacolon from patients with chronic Chagas' disease.

PURPOSE: The mechanisms that control chronic infection in vivo and the immunologic mechanisms involved in the pathogenesis of chagasic megacolon are not completely characterized. Although autoimmunity may play a role in the pathogenesis of Chagas' disease, recent studies, both in mice and in humans, suggest a positive association of tissue parasitism, inflammation, and severity of lesions. The aim of this study was to evaluate the role of inflammatory cells and the subclasses of lymphocytes involved in neuropathic lesions in the colon of patients who underwent resection for advanced megacolon. METHODS: Specimens from 23 patients were selected based on histopathologic analysis. Paraffin-embedded tissue blocks were sectioned and evaluated by immunohistochemistry for cluster of differentiation 3, cluster of differentiation 8, cluster of differentiation 20, and natural killer cell antibodies by an avidin-biotin peroxidase method. RESULTS: Almost all myenteric plexuses were damaged, characterized by degenerative changes, necrosis of ganglion cells, and inflammatory response. Mild lymphocytic infiltration around degenerated and normal ganglion cells was observed in all cases. Collagen fibers and mononuclear cells surrounded some ganglion cells. Most of the inflammatory cells were lymphocytes, identified as cluster of differentiation 3-positive cells. Cluster of differentiation 8-positive lymphocytes were associated with degenerated ganglion cells. Natural killer cell antibodies were detected in a lower proportion of cells and were distributed between muscle layers or in proximity to the myenteric plexus. All these findings were also observed in the submucosal plexus. Cluster of differentiation 20-positive lymphocytes were not present in muscle layers or in the vicinity of either plexus. CONCLUSION: Pathogenesis of the megacolon is based on a continuous process of ganglion cell damage with participation of T lymphocytes expressing cluster of differentiation 8 and natural killer cell membrane antigens. B lymphocytes do not take part in the chronic inflammatory reaction.