Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Immunology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
Parasitol Res. 2021 Apr;120(4):1151-1166. doi: 10.1007/s00436-021-07070-6. Epub 2021 Feb 3.
The mechanistic (or mammalian) target of rapamycin (mTOR) is considered as a critical regulatory enzyme involved in essential signaling pathways affecting cell growth, cell proliferation, protein translation, regulation of cellular metabolism, and cytoskeletal structure. Also, mTOR signaling has crucial roles in cell homeostasis via processes such as autophagy. Autophagy prevents many pathogen infections and is involved on immunosurveillance and pathogenesis. Immune responses and autophagy are therefore key host responses and both are linked by complex mTOR regulatory mechanisms. In recent years, the mTOR pathway has been highlighted in different diseases such as diabetes, cancer, and infectious and parasitic diseases including leishmaniasis, toxoplasmosis, and malaria. The current review underlines the implications of mTOR signals and intricate networks on pathogen infections and the modulation of this master regulator by parasites. Parasitic infections are able to induce dynamic metabolic reprogramming leading to mTOR alterations in spite of many other ways impacting this regulatory network. Accordingly, the identification of parasite effects and interactions over such a complex modulation might reveal novel information regarding the biology of the abovementioned parasites and might allow the development of therapeutic strategies against parasitic diseases. In this sense, the effects of inhibiting the mTOR pathways are also considered in this context in the light of their potential for the prevention and treatment of parasitic diseases.
雷帕霉素的哺乳动物靶标（mTOR）被认为是一种关键的调节酶，参与影响细胞生长、细胞增殖、蛋白质翻译、细胞代谢调节和细胞骨架结构的基本信号通路。此外，mTOR 信号在通过自噬等过程的细胞稳态中起着至关重要的作用。自噬可以预防许多病原体感染，并参与免疫监视和发病机制。因此，免疫反应和自噬是宿主的关键反应，两者都通过复杂的 mTOR 调节机制联系在一起。近年来，mTOR 途径在糖尿病、癌症以及包括利什曼病、弓形虫病和疟疾在内的感染性和寄生虫病等不同疾病中得到了强调。本综述强调了 mTOR 信号及其复杂网络对病原体感染的影响，以及寄生虫对该主调节因子的调节。寄生虫感染能够诱导动态代谢重编程，导致 mTOR 改变，尽管还有许多其他方式影响这个调节网络。因此，识别寄生虫对这种复杂调节的影响和相互作用可能会揭示上述寄生虫生物学的新信息，并可能为寄生虫病的治疗策略的发展提供依据。在这方面，还考虑了抑制 mTOR 途径的效果，因为它们可能具有预防和治疗寄生虫病的潜力。
