Papel de SOCS2 na resposta imune e função cardíaca durante a infecção experimental por Trypanosoma cruzi

Detalhes bibliográficos
Ano de defesa: 2011
Autor(a) principal: Lisia Maria Esper
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Minas Gerais
UFMG
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://hdl.handle.net/1843/BUOS-8TFKKH
Resumo: Infection with Trypanosoma cruzi induces robust inflammation that limits parasite proliferation but may result in Chagas heart disease. The 5-Lipoxygenase pathway induces suppressor of cytokine signaling(SOCS)2 expression, an important regulator of immuneresponses. Here, we investigated the role of SOCS2 for the pathogenesis of T. cruzi infection. We investigated the expression of SOCS2 in wild type, 5-LO knockout-(KO) and SOCS2-KO mice during infection and its effects on the development of the immune response and cardiac pathology. There was reduction of parasitemia and expression of IFN-, TNF-, IL-6, IL-10, SOCS1 and SOCS3 in the spleen and IFN-, TNF-, SOCS1and SOCS3 in the heart of infected SOCS2-KO mice. Additionally, there was an increase Lipoxina A4 and generation/expansion of T regulatory and a decrease of memory cells in T. cruzi-infected SOCS2KO. Electrophysiological/echocardiographic analyses showed animpairment of cardiac function in T. cruzi-infected SOCS2-KO mice, which was due in part to a disturbance of calcium handling, changes in action potential waveform and reduced outward potassium current in isolated cardiomyocytes. SOCS2 deficiency results in reduced inflammatory response and better control of infection, which is secondary to increased LXA4 and Treg cells induction. This occurs at the cost of greater infection-associated heart dysfunction, highlighting the relevance ofbalanced inflammatory and immune responses in preventing severe disease in the context of T. cruzi infection.