Impact of IFN-gamma Deficiency on the Cardiomyocyte Function in the First Stage of Experimental Chagas Disease

Autor(es)

Roman-Campos, Danilo ; Sales-Junior, Policarpo ; Costa, Alexandre D. ; Souza, Diego Santos ; Santos-Miranda, Artur ; Joviano-Santos, Julliane, V ; Ropert, Catherine ; Cruz, Jader S.

• Tipo de documento: Artigo Científico
• Fonte: MICROORGANISMS; v. 10, n. 2, p. 7-pg., 2022-02-01.

Resumo

Chagas disease (CD) is caused by the parasitic protozoan T. cruzi. The progression of CD in similar to 30% of patients results in Chagasic Cardiomyopathy (CCM). Currently, it is known that the inflammatory system plays a significant role in the CCM. Interferon-gamma (IFN-gamma) is the major cytokine involved in parasitemia control but has also been linked to CCM. The L-type calcium current (I-Ca,I-L) is crucial in the excitation/contraction coupling in cardiomyocytes. Thus, we compared I-Ca,I-L and the mechanical properties of cardiomyocytes isolated from infected wild type (WT) and IFN-gamma((-/-)) mice in the first stage of T. cruzi infection. Using the patch clamp technique, we demonstrated that the infection attenuated I-Ca,I-L in isolated cardiomyocytes from the right and left ventricles of WT mice at 15 days post-infection (dpi), which was not observed in the IFN-gamma((-/-)) cardiomyocytes. However, I-Ca,I-L was attenuated between 26 and 30 dpi in both experimental groups. Interestingly, the same profile was observed in the context of the mechanical properties of isolated cardiomyocytes from both experimental groups. Simultaneously, we tracked the mortality and MCP-1, TNF-alpha, IL-12, IL-6, and IL-10 serum levels in the infected groups. Importantly, the IFN-gamma((-/-)) and WT mice presented similar parasitemia and serum inflammatory markers at 10 dpi, indicating that the modifications in the cardiomyocyte functions observed at 15 dpi were directly associated with IFN-gamma((-/-)) deficiency. Thus, we showed that IFN-gamma plays a crucial role in the electromechanical remodeling of cardiomyocytes during experimental T. cruzi infection in mice. (AU)

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