Roy Souravi, Mandal Mayumi, Halder Moumita, Das Pijush K, Ukil Anindita
Department of Biochemistry, https://ror.org/01e7v7w47University of Calcutta, Kolkata, India.
Infectious Diseases and Immunology Division, https://ror.org/01kh0x418CSIR - Indian Institute of Chemical Biology, Kolkata, India.
Expert Rev Mol Med. 2025 Jun 20;27:e21. doi: 10.1017/erm.2025.10010.
Reactive oxygen species (ROS) play a dual role in leishmaniasis by contributing to both host defence and parasite survival mechanisms. In the host, ROS promote parasite clearance through induction of apoptosis, activation of pro-inflammatory signalling pathways (e.g., MAPK, JNK), inflammasome assembly, and M1 macrophage polarisation. Conversely, Leishmania species have evolved multiple strategies to neutralize ROS, including the upregulation of host antioxidant enzymes like HO-1, inhibition of ROS-producing pathways, and expression of parasite-derived antioxidants such as SOD, GPx, and trypanothione reductase. The parasite alsoadapts through gene regulation and metabolic changes to counter oxidative stress. Importantly, ROS have emerged as key targets for antileishmanial therapies, with various drugs and natural compounds shown to induce ROS-mediated parasite death, highlighting their potential in future therapeutic development.
In summary, the survival of Leishmania hinges on its ability to counteract host-induced oxidative stress. Targeting its antioxidant defences and enhancing host ROS production can disrupt this balance, leading to parasite death. Exploring ROS-related signalling offers a promising path for developing effective therapies against leishmaniasis.
活性氧（ROS）在利什曼病中发挥双重作用，既有助于宿主防御机制，也有助于寄生虫的生存机制。在宿主体内，ROS通过诱导细胞凋亡、激活促炎信号通路（如MAPK、JNK）、炎性小体组装和M1巨噬细胞极化来促进寄生虫清除。相反，利什曼原虫物种已经进化出多种策略来中和ROS，包括上调宿主抗氧化酶如HO-1、抑制ROS产生途径以及表达寄生虫衍生的抗氧化剂如SOD、GPx和锥虫硫醇还原酶。寄生虫还通过基因调控和代谢变化来适应氧化应激。重要的是，ROS已成为抗利什曼病治疗的关键靶点，各种药物和天然化合物已显示可诱导ROS介导的寄生虫死亡，突出了它们在未来治疗开发中的潜力。
总之，利什曼原虫的生存取决于其对抗宿主诱导的氧化应激的能力。靶向其抗氧化防御并增强宿主ROS产生可破坏这种平衡，导致寄生虫死亡。探索与ROS相关的信号传导为开发有效的抗利什曼病疗法提供了一条有前景的途径。
