Aspectos imunorregulatórios nas fases aguda e crônica recente da doença de Chagas: expressão de citocinas e análise de potencial citotóxico

• Ano de defesa: 2012
• Autor(a) principal: Daniela Valente Andrade
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Biologia Celular; Citologia
• Link de acesso: http://hdl.handle.net/1843/BUOS-8YJK55

Chagas disease is an infectious disease caused by the protozoan Trypanosoma cruzi that affects approximately 10 million people. Once a neglected disease from poor areas in Latin American countries, it has now spread to nonendemic areas due to globalization, bringing Chagas disease to a global threat status. Despite high mortality and morbidity rates, patients are challenged by the lack of a specific effective therapy and biomarkers of disease progression. Considering the range of immunological events elicited during acute infection and its association with distinct clinical aspects and disease outcome, the understanding of cell populations and molecules are a very attractive lead for development of a successful immunotherapy. Considering this, our cutting-edge work aims to identify specific cell populations and/or cytokines elicited during the acute phase that could be determinant to disease evolution towards a protective or pathological condition in the cronic phase. We compared the imunological profiles of patients in the acute phase and after they entered the chronic phase, at an early stage. Considering that major T cell populations play an important role in the immunopathology of human Chagas disease, we evaluated the frequency of CD4+, CD8+ and TCD4-CD8- (double negative - DN) T cells in acute Chagasic patients (Chg) and non-infected individuals (NI). Similar frequencies of these cell populations between Chg and NI groups were observed. Induction of effector mechanisms by T cells is extensively dependent on their activation profile, which was evaluated by the expression of the surface molecule HLA-DR. We demonstrated that Chg display higher levels CD4+HLA-DR+ compared to NI. Following T cell activation, establishment of immune responses directed against T. cruzi infection is extensively based on the fine balance of inflammatory and anti-inflammatory cytokines. We observed that DN T cells are compromised with production of IFN- and IL-10 in acute chagasic patients. In conjunction with cytokines, we evaluated the involvement of cytotoxic events in the immune responses against T. cruzi infection. By analyzing the expression oh Granzyme A in CD8+ T cells, we demonstrated that, although there is no expansion of CD8+GranA+ cells in Chg compared to NI, expression of the inflammatory cytokines TNF- and IL1- in CD8+Granzyme A+ cells was higher in the first group. In our follow-up study, we compared the immunological profile of chagasic patients in the acute (Ac) and chronic (Chr) phase. As disease progresses to chronic phase, we observed a lower frequency of CD8+ IFN-.This data, altogether, show an activated immune profile of patients in acute phase and as disease progresses, cell populations with distinct functional could be controlling an exacerbated inflammatory response.