Roman-Campos Danilo, Sales-Junior Policarpo, Costa Alexandre D, Souza Diego Santos, Santos-Miranda Artur, Joviano-Santos Julliane V, Ropert Catherine, Cruz Jader S
Laboratório de Cardiobiologia, Department of Biophysics, Federal University of São Paulo, São Paulo 04021, Brazil.
Oswaldo Cruz Foundation, Eusébio 61760, Brazil.
Microorganisms. 2022 Jan 25;10(2):271. doi: 10.3390/microorganisms10020271.
Chagas disease (CD) is caused by the parasitic protozoan 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 (I) is crucial in the excitation/contraction coupling in cardiomyocytes. Thus, we compared I and the mechanical properties of cardiomyocytes isolated from infected wild type (WT) and IFN-γ mice in the first stage of infection. Using the patch clamp technique, we demonstrated that the infection attenuated I 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, I 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 infection in mice.
恰加斯病（CD）由寄生原生动物引起。约30%的CD患者病情进展会导致恰加斯性心肌病（CCM）。目前已知，炎症系统在CCM中起重要作用。γ干扰素（IFN-γ）是参与控制寄生虫血症的主要细胞因子，但也与CCM有关。L型钙电流（I）在心肌细胞的兴奋/收缩偶联中起关键作用。因此，我们比较了感染野生型（WT）小鼠和IFN-γ基因敲除小鼠在感染第一阶段分离的心肌细胞的I和力学特性。使用膜片钳技术，我们证明感染使WT小鼠感染后15天（dpi）左右心室分离的心肌细胞中的I减弱，而在IFN-γ基因敲除小鼠的心肌细胞中未观察到这种情况。然而，在两个实验组中，I在26至30 dpi之间减弱。有趣的是，在两个实验组分离的心肌细胞力学特性方面也观察到了相同的情况。同时，我们追踪了感染组的死亡率以及MCP-1、TNF-α、IL-12、IL-6和IL-10的血清水平。重要的是，IFN-γ基因敲除小鼠和WT小鼠在10 dpi时呈现相似的寄生虫血症和血清炎症标志物，表明在15 dpi时观察到的心肌细胞功能改变与IFN-γ缺乏直接相关。因此，我们表明IFN-γ在小鼠实验性感染期间心肌细胞的电机械重塑中起关键作用。
