RESUMO
Experimental models of Schistosoma mansoni infections in mammals have contributed greatly to our understanding of the pathology and pathogenesis of infection. We consider here hepatic and extrahepatic disease in models of acute and chronic infection. Experimental schistosome infections have also contributed more broadly to our understanding of granulomatous inflammation and our understanding of Th1 versus Th2 related inflammation and particularly to Th2-mediated fibrosis of the liver.
Assuntos
Modelos Animais de Doenças , Granuloma/imunologia , Schistosoma mansoni , Esquistossomose mansoni/imunologia , Doença Aguda , Animais , Doença Crônica , Granuloma/parasitologia , Granuloma/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/parasitologia , Cirrose Hepática/patologia , Hepatopatias Parasitárias/imunologia , Hepatopatias Parasitárias/parasitologia , Hepatopatias Parasitárias/patologia , Esquistossomose mansoni/patologia , Especificidade da Espécie , Células Th1/imunologia , Células Th2/imunologiaRESUMO
Experimental models of Schistosoma mansoni infections in mammals have contributed greatly to our understanding of the pathology and pathogenesis of infection. We consider here hepatic and extrahepatic disease in models of acute and chronic infection. Experimental schistosome infections have also contributed more broadly to our understanding of granulomatous inflammation and our understanding of Th1 versus Th2 related inflammation and particularly to Th2-mediated fibrosis of the liver
Assuntos
Animais , Modelos Animais de Doenças , Granuloma , Schistosoma mansoni , Esquistossomose mansoni , Doença Aguda , Doença Crônica , Granuloma , Fígado , Mamíferos , Esquistossomose mansoni , Células Th1 , Células Th2RESUMO
Schistosoma mansoni infections are associated with a strong Th2 cytokine response. Treatment of mice with IL-12 or anti-IL-2 or anti-IL-4 before i.v. injection of eggs increased IFN-gamma production and downregulated Th2 responses and pulmonary granuloma size. Conversely, anti-IFN-gamma antibody treatment increased Th2 responses and granoloma size. Similar manipulation produced less dramatic results in infected mice. However, sensitization of mice with eggs + IL-12 before infection augmented the Th1 response and decreased Th2 cytokines, granoloma size and fibrosis. Antisera to IFN-gamma, TNF-alpha or IL-12 during IL-12-egg immunization partly restored granuloma size and fibrosis following infection. Variations in the size of granulomas in acute (8 weeks) infections may be influenced primarily by the number and state of activation of T cells. In chronic (12-16 week) infections immunologic downmodulation proceed normally in mice without functional CD8 + cells and in IFN-gamma KO mice but not in B cell KO (µMT) mice or in mice deficient in FcR expression in spite of the fact that these mice downregulated their T cell and cytokine responses. It is evident that the participation of cytokines in granuloma formation and regulation is complicated and that the mechanisms controlling both these phenomena are likely to involve both T cells and antibody/FcR interactions.
Assuntos
Animais , Ratos , Cirrose Hepática/parasitologia , Citocinas , Fígado/parasitologia , Granuloma/parasitologia , Esquistossomose mansoni/veterinária , /parasitologia , Camundongos/parasitologiaRESUMO
Granuloma size is the variable most frequently used to evaluate the immunopathogenesis of schistosome infections. However, hepatic fibrosis is at the least an equally relevant variable. Hepatic fibrosis and the size of circumoval granulomas are frequently dissociated in experimental murine Schistosoma mansoni and S. japonicum infections. Virtually nothing is known of the immunoregulation of schistosomal hepatic fibrosis. This review notes many of the studies which have found discrepancies in granuloma volume and hepatic fibrosis, attempts to put them in perspective and to evaluate methods of calculating changes in collagen synthesis or content.
Assuntos
Cirrose Hepática/parasitologia , Granuloma/parasitologia , Schistosoma/patogenicidadeRESUMO
Cytokines are important in the cell-mediated response to Schistosoma mansoni eggs. We have found that Th2 cytokine responses (e.G. IL-4 and IL-5) are argumented after egg laying begins while the response (IL-2 and IFN-*) are down regulated in S. mansoni infected mice. Treatment of mice with anti-IL-5 monoclonal antibodies (Mab) suppressed the eosinophil response almost completley but did not affect granuloma size and slightly increased hepatic fibrosis. Anti-IL-4 treatment abolished IgE responses in infected mice and decreased hepatic fibrosis slightly. Anti-IFN-* treatment had no effect on hepatic pathology. Anti-IL-2 treatment decreased granuloma size significantly and decreased hepatic fibrosis markedly. Anti-IL-2 treatment dramatically decreased IL-5 secretion by splenic cells in vitro and decreased peripheral blood and tissue eosinophilia. In contrast IL-4 secretion was unaffected and serum IgE was normal or increased. IL-2 and IFN-* secretion by splenic cells of treated mice were slightly but not significantly increased suggesting that anti-IL-2 treatment affecting Th2 rather than Th1 responses
Assuntos
Anticorpos Monoclonais , Interleucinas , Schistosoma mansoni/patogenicidadeRESUMO
In this paper a discussin is made on the pathogenesis of schistosomiasis mansoni in mice, presented from the perspectives of "processes", "mediators", "strategies for study" and vasculitis are discussed. The role of mediators, including cells, antibodies and immune complexes, cytokines and distal mediators is commented as related to the pathological processes occuring in schistosomiasis. Finally, strategies for study are presented, followed by a discussion on the etiopathogenesis of the different clinical stages and pathologic manifestations of schistosomiasis mansoni
Assuntos
Ratos , Schistosoma mansoni/patogenicidade , Esquistossomose mansoniRESUMO
The hepatic, intestinal and cardiopulmonary lesions produced by Schistosoma mansoni, S. haematobium and S. japonicum in man and experimental animals often bear striking similarities but usually have distinctive features as well. These are often related to parasitologic differences. Thus S. japonicum and S. haematobium lay their eggs in clusters which elicit the formation of large composite granulomas. The worms of these two species also tend to be sedentary, remaining in a single location for prolonged periods, thus producing large focal lesions in the intestines or urinary tract. Worm pairs of these two species also are gregarious and many worm pairs are often found in a single lesion. The size of circumoval granulomas, and the degree of fibrosis, are T cell dependent. The modulation of granuloma size is largely T cell dependent in mice infected with S. mansoni but is mostly regulated by serum factors in S. japonicum infected mice. In spite of these differences in egg laying and immunoregulation both S. mansoni and S. japonicum produce Symmers' fibrosis in the chimpanzee while S. haematobium does not, despite the presence of numerous eggs in the liver.
Assuntos
Humanos , Animais , Camundongos , Esquistossomose mansoni , Esquistossomose Urinária , Esquistossomose Japônica , Pan troglodytes , Granuloma , Intestinos/parasitologia , Miocárdio/patologiaRESUMO
Mice were killed 7, 11, 19, and 27 weeks after infection with strains of Schistosoma mansoni from Puerto Rico, Brazil, St Lucia, and Tanzania. The percentage recovery of adult worms was variable in different experiments and no consistent strain differences were observed. The prepatient period was prolonged in mice infected with the Mwanza strain. Significant differences were noted in the number of eggs per worm pair in the tissues, in the distribution of eggs in the tissues, and in the weight of liver of mice infected with different strains. No differences in hepatic histopathology were detected. Although the behaviour of various worms in this mammalian host is clearly different, we feel that the observed differences are trivial when considering the effects of the parasite on the host, and that the result in mice probably cannot be used to predict possible differences in the behaviour of geographical strains of S. mansoni in infected persons (AU)