Infection by Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, depends on reactive oxygen species (ROS), which has been described to induce parasite proliferation in mammalian host cells. It is unknown how the parasite manages to increase host ROS levels. Here, we found that intracellular T. cruzi forms release in the host cytosol its major cyclophilin of 19 kDa (TcCyp19). Parasites depleted of TcCyp19 by using CRISPR/Cas9 gene replacement proliferate inefficiently and fail to increase ROS, compared to wild type parasites or parasites with restored TcCyp19 gene expression. Expression of TcCyp19 in L6 rat myoblast increased ROS levels and restored the proliferation of TcCyp19 depleted parasites. These events could also be inhibited by cyclosporin A, (a cyclophilin inhibitor), and by polyethylene glycol‐linked to antioxidant enzymes. TcCyp19 was found more concentrated in the membrane leading edges of the host cells in regions that also accumulate phosphorylated p47^phox, as observed to the endogenous cyclophilin A, suggesting some mechanisms involved with the translocation process of the regulatory subunit p47^phox in the activation of the NADPH oxidase enzymatic complex. We concluded that cyclophilin released in the host cell cytosol by T. cruzi mediates the increase of ROS, required to boost parasite proliferation in mammalian hosts.

中文翻译：

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克氏锥虫在宿主细胞胞质溶胶中分泌的亲环蛋白 19 促进寄生虫生长所需的 ROS 产生

克氏锥虫（一种导致恰加斯病的原生动物寄生虫）的感染取决于活性氧 (ROS)，它已被描述为诱导哺乳动物宿主细胞中的寄生虫增殖。目前尚不清楚寄生虫如何设法增加宿主 ROS 水平。在这里，我们发现细胞内的T. cruzi在宿主细胞质中释放其主要的 19 kDa ( Tc Cyp19) 亲环蛋白。与野生型寄生虫或具有恢复的Tc Cyp19 基因表达的寄生虫相比，通过使用 CRISPR/Cas9 基因替换耗尽Tc Cyp19 的寄生虫增殖效率低且无法增加 ROS。Tc的表达L6 大鼠成肌细胞中的 Cyp19 增加了 ROS 水平并恢复了Tc Cyp19 耗尽的寄生虫的增殖。这些事件也可以被环孢菌素 A（一种亲环素抑制剂）和与抗氧化酶连接的聚乙二醇抑制。发现Tc Cyp19 更集中在宿主细胞的膜前缘中也积累磷酸化 p47 ^{phox的区域，正如对内源性亲环蛋白 A 所观察到的那样，这表明调节亚基 p47 phox}在激活中的易位过程涉及一些机制。 NADPH 氧化酶酶复合物。我们得出结论，T. cruzi在宿主细胞胞质溶胶中释放了亲环素介导 ROS 的增加，这是促进哺乳动物宿主中寄生虫增殖所必需的。