Caracterização da resposta imunológica e patológica induzida pela proteína IPSE/alpha-1, secretada pelo ovo do Schistosoma mansoni, em camundongos C57BL/6

• Ano de defesa: 2008
• Autor(a) principal: Julia Silveira Fahel
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Schistosoma mansoni; Schistossoma mansoni; Bioquímica
• Link de acesso: http://hdl.handle.net/1843/CMFC-7LDN36

Schistosomiasis is a tropical parasitic disease caused by helminths of the genus Schistosoma. During S. mansoni infection, eggs deposited by female worm in mesenteric veins can be pushed by blood flow and get trapped mainly in livers sinusoid capilarries. In this environment, egg secretes antigens that induce granuloma development. IPSE/alpha-1 is one of the most abundant proteins in S. mansoni egg secretions. The aim of this work is the evaluation of the immunological and pathological response induced by recombinant IPSE/alpha-1 in C57BL/6 mice. Recombinant IPSE/alpha-1 was expressed in Escherichia coli as a His tag fusion protein. C57BL/6 mice were immunized with IPSE/alpha-1r or PBS as control. Production of specific antibodies were analysed in mice sera by ELISA. Immunization with IPSE/alpha-r induced the production of high levels of total IgG, IgG1 and IgG2a. The production of IgG1 was the most relevant. Splenocytes from immunized were incubated with the recombinant protein. The production of high levels of IFN-, TNF-, IL-5 and IL-13 was detected by ELISA. Immunized mice were infected with S. mansoni and seven weeks post-infection liver fragments were collected. The number of eggs and granulomas, granulomas total area and fibrosis area were analysed by morphometry. Additionally granulomas were categorized into three stages of maturation based on cellularity and fibrosis level and the prevalence of the stages were analyzed. Except for granulomas total area, no alteration in the other parameters was detected. IPSE/alpha-1 immunized mice developed 25% larger granulomas compared to control group. In addition the increase in the granuloma area was limited to the third stage of maturation. The eosinophil and macrophage infiltration into the hepatic tissue was determined by eosinophil peroxidase (EPO) and n-acetyl--glucosaminidase (NAG) assays, respectively. No alteration of EPO activity was detected. Conversely, NAG activity was higher in IPSE/alpha-1r immunized and infected mice. Levels of CCL2, CCL3, CCL5 and CCL11 were measured in supernatants of macerated tissue by ELISA. However no significant alterations in the production of these chemokines were detected. These results shows that immunization with IPSE/alpha-1r induces a Th1/Th2 type of immune response in C57BL/6 mice and an increase in hepatic granuloma in the third stage of maturation. This enlargement is partially due to a higher macrophage infiltration.