Bovine tropical theileriosis is a tick-borne disease, caused by Theileria annulata which is a protozoan parasite that resides within the B-cells and macrophages. T. annulata is a unique parasite that can transform bovine leucocytes which leads to the cancer hallmarks in the infected cells. Previously, curcumin has been shown to possess multiple pharmacological activities such as anti-inflammatory and anti-cancer activities. In this study, we demonstrated that curcumin inhibits the proliferation of Theileria-transformed bovine leucocytes by promoting apoptosis and autophagy. The transcriptome analysis of curcumin treated cells showed that the genes involved in cell death and autophagy are also differentially regulated. We further elucidated the mechanism of action of curcumin on Theileria infected bovine cells. We found that curcumin induced the generation of reactive oxygen species (ROS) which activated caspase 8 and destabilized the mitochondrial membrane potential leading to the release of cytochrome c from mitochondria. This subsequently led to the activation of caspase 3 and PARP cleavage, finally leading to apoptosis in the infected cells. Furthermore, curcumin induced the process of autophagy which was characterized by the formation of acidic vesicular organelles, LC3B accumulation with lysosome inhibitor, E64d, and the presence of autophagosomes as visualized by transmission electron microscopy (TEM). Curcumin treatment suppressed the mTOR and increased the expression of autophagy-related proteins. We also found that N- acetylcysteine, an inhibitor of ROS, could rescue the infected cells from curcumin induced apoptosis and autophagy mediated cell death. Intriguingly, curcumin had no effect on uninfected bovine PBMCs. Altogether, these data suggest the therapeutic potential of curcumin against bovine tropical theileriosis.

牛热带性麻疯病是由tick传播的疾病，由Theileria annulata引起，后者是一种生活在B细胞和巨噬细胞内的原生动物寄生虫。圆环虫是一种独特的寄生虫，可以转化牛白细胞，从而在被感染的细胞中导致癌症。以前，姜黄素已显示出具有多种药理活性，例如抗炎和抗癌活性。在这项研究中，我们证明了姜黄素抑制泰勒虫的增殖促进细胞凋亡和自噬，转化牛白细胞。姜黄素处理过的细胞的转录组分析表明，参与细胞死亡和自噬的基因也受到不同的调控。我们进一步阐明了姜黄素对泰勒氏菌的作用机理被感染的牛细胞。我们发现姜黄素诱导了活性氧（ROS）的生成，从而激活了胱天蛋白酶8，并使线粒体膜电位不稳定，从而导致线粒体中细胞色素c的释放。随后导致胱天蛋白酶3的活化和PARP的切割，最终导致被感染细胞的凋亡。此外，姜黄素诱导自噬过程，其特征在于形成酸性水泡细胞器，LC3B与溶酶体抑制剂，E64d积累，以及通过吞噬电子显微镜（TEM）观察到的自噬体的存在。姜黄素处理抑制mTOR，并增加自噬相关蛋白的表达。我们还发现ROS抑制剂N-乙酰半胱氨酸 可以从姜黄素诱导的细胞凋亡和自噬介导的细胞死亡中拯救受感染的细胞。有趣的是，姜黄素对未感染的牛PBMC没有影响。总而言之，这些数据表明姜黄素对牛热带麻疯病的治疗潜力。