Estudo imunológico e histopatológico da infecção experimental por Schistosoma mansoni em camundongos geneticamente selecionados para tolerância oral

Abstract

Schistosomiasis affects 207 million people, with more than 200 000 deaths annually. Its main etiological agent is the helminth Schistosoma and the main experimental model, the mouse. Strains of mice genetically selected for susceptibility (TS) and resistance (TR) immunological tolerance are good models for the study of specific and nonspecific immune response in infections. The objective of this study was to characterize the experimental infection with S. mansoni in these mice, demonstrating the immunopathology of several parameters in the acute phase of infection. TR and TS did not differ in the penetration of cercariae, adult worms recovery, fecundity/ productivity of eggs from females of S. mansoni, but dead eggs prevailed in TS. The greater the number of couples, the more probability of changing couples and female sexual regression, and slight reduction of the eggs productivity. Ultrastructural analysis of parasites recovered from TS males had swollen tubercles, shortened spines and lower density of them than the parasites of TR. The tegument of the parasites recovered from TS appeared disorganized, intensely vacuolated and with a tendency to detach from the surface and internalized spines and disorganized vitelline cells. TS developed large hepatic granulomas with radial fibers and predominance of exudative-productive stage with characteristics of productive stage (EP/P), while TR mice developed smaller granulomas, with concentric fibers and predominance of exudative-productive granulomas. TS developed hepatomegaly more pronounced in the acute phase of infection and exacerbated splenomegaly in chronic phase. The aspartate aminotransferase was higher in TR mice consistent with the marked histolysis in initials TR granulomas. It is possible that the lower histolysis in TS mice has contributed to its severe hepatomegaly in acute phase. Serum total leukocytes increased in TS acute and chronic phases, but not in TR. TS had anemia during the chronic phase of infection, possibly due to deviation in bone marrow hematopoiesis for the production of leukocytes or apoptosis of red blood cells. The neutrophil myeloperoxidase from liver and ileum were higher in TS and the eosinophil peroxidase was higher in the TS ileum. Both strains produced IFN-γ, but functional levels of IFN-γ were different in the two strains in cell culture. It is possible that severe liver immunopathology in TS strain may to be related to high IFN-γ titers. TS produced IL-10 in larger quantities, however this cytokine was not able to regulate the overgrowth of hepatic granulomas. High levels of IL-4 in TS strain are also consistent with the exacerbation of granulomas, because as IL-13, IL-4 induces collagen synthesis and is related to the development of fibrosis in schistosomal granuloma. We observed reduction in the relative percentage of TCD4 + liver cells of infected animals in both strains and percentage reduction in subpopulations of B lymphocytes in bone marrow (precursors, immature and mature B lymphocytes, plasma cells) stronger in TS than TR, possibly due to extensive mobilization of immature B cells induced by inflammation or hematopoiesis deviation for synthesis of granulocytes in TS. Quantitatively, TR did not change their subpopulations of B lymphocytes. TS and TR are good models for studying the immune response in experimental schistosome infection. Further studies are needed to confirm our proposals and to understand the mechanisms underlying the difference in immune response of these strains in the relationship schistosoma-host.