Abstract
Chagas disease (CD) is caused by the parasitic protozoan T. cruzi. The progression of CD in ~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-γ) is the major cytokine involved in parasitemia control but has also been linked to CCM. The L-type calcium current (ICa,L) is crucial in the excitation/contraction coupling in cardiomyocytes. Thus, we compared ICa,L and the mechanical properties of cardiomyocytes isolated from infected wild type (WT) and IFN-γ(−/−) mice in the first stage of T. cruzi infection. Using the patch clamp technique, we demonstrated that the infection attenuated ICa,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-γ(−/−) cardiomyocytes. However, ICa,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-α, IL-12, IL-6, and IL-10 serum levels in the infected groups. Importantly, the IFN-γ(−/−) 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-γ(−/−) deficiency. Thus, we showed that IFN-γ plays a crucial role in the electromechanical remodeling of cardiomyocytes during experimental T. cruzi infection in mice.
Highlights
Laboratório de Cardiobiologia, Department of Biophysics, Federal University of São Paulo, Laboratório de Membranas Excitáveis e de Biologia Cardíaca, Department of Biochemistry and Immunology, Abstract: Chagas disease (CD) is caused by the parasitic protozoan T. cruzi
We showed that a global absence of IFN-γ during T. cruzi infection
IFN-γ production has been consistently associated with altered cardiomyocyte function in the acute phase of experimental CD [10] and with heart malfunction in the chronic phase of CD in humans [6,7]
Summary
We compared ICa,L and the mechanical properties of cardiomyocytes isolated from infected wild type (WT) and IFNγ(−/−) mice in the first stage of T. cruzi infection. Using the patch clamp technique, we demonstrated that the infection attenuated ICa,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-γ( −/− ) cardiomyocytes. We showed that IFN-γ plays a crucial role in the electromechanical remodeling of cardiomyocytes during experimental T. cruzi infection in mice. Innate and adaptive immune responses are critical for infection control, and the connection between these responses is mainly orchestrated by cytokines. In this regard, the interferon-γ (IFN-γ) type II subfamily plays a vital role [4].
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