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

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

20/12/2011

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 immune responses. 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-, SOCS1 and 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 an impairment 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 of balanced inflammatory and immune responses in preventing severe disease in the context of T. cruzi infection.

ASSUNTO(S)

medicina tropical teses. chagas, doença de teses. doença de chagas/prevenção &controle decs doença de chagas/imunologia decs trypanosoma cruzi/patogenicidade decs citocinas/imunologia decs citocinas/deficiência decs cardiomiopatia chagásica/fisiopatologia decs experimentação animal decs camundongos decs dissertações acadêmicas decs

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