Unidad de Investigación, División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Departamento de Microbiología, Centro de Investigación en Ciencias de la Salud, Facultad de Ciencias de la Salud Universidad Anáhuac México Norte, Huixquilucan, Estado de México, Mexico.
Arch Med Res. 2024 Sep;55(6):103041. doi: 10.1016/j.arcmed.2024.103041. Epub 2024 Jul 11.
Leishmaniasis is a relevant disease worldwide due to its presence in many countries and an estimated prevalence of 10 million people. The causative agent of this disease is the obligate intracellular parasite Leishmania which can infect different cell types. Part of its success depends on its ability to evade host defense mechanisms such as apoptosis. Apoptosis is a finely programmed process of cell death in which cells silently dismantle and actively participate in several processes such as immune response, differentiation, and cell growth. Leishmania has the ability to delay its initiation to persist in the cell. It has been well documented that different Leishmania species target different pathways that lead to apoptosis of cells such as macrophages, neutrophils, and dendritic cells. In many cases, the observed anti-apoptotic effect has been associated with a significant reduction in caspase-3 activity. Leishmania has also been shown to target several pathways involved in apoptosis such as MAPK, PI3K/Akt, and the antiapoptotic protein Bcl-xL. Understanding the strategies used by Leishmania to subvert the defense mechanisms of host cells, particularly apoptosis, is very relevant for the development of therapies and vaccines. In recent years, the drug artemisinin has been shown to be effective against several parasitic diseases. Its role against Leishmania may be promising. In this review, we provide important aspects of the disease, the strategies used by the parasite to suppress apoptosis, and the role of artemisinin in Leishmania infection.
利什曼病是一种在世界范围内具有重要意义的疾病,因为它存在于许多国家,估计有 1000 万人感染。这种疾病的病原体是专性细胞内寄生虫利什曼原虫,它可以感染不同的细胞类型。其部分成功取决于它逃避宿主防御机制的能力,如细胞凋亡。细胞凋亡是一种细胞死亡的精细编程过程,其中细胞默默地拆卸并积极参与免疫反应、分化和细胞生长等几个过程。利什曼原虫有能力延迟其启动以在细胞中持续存在。已经有充分的文献记载,不同的利什曼原虫物种针对导致巨噬细胞、中性粒细胞和树突状细胞等细胞凋亡的不同途径。在许多情况下,观察到的抗细胞凋亡作用与 caspase-3 活性的显著降低有关。利什曼原虫还被证明针对参与细胞凋亡的几种途径,如 MAPK、PI3K/Akt 和抗凋亡蛋白 Bcl-xL。了解利什曼原虫用来颠覆宿主细胞防御机制的策略,特别是细胞凋亡,对于开发疗法和疫苗非常重要。近年来,青蒿素类药物已被证明对几种寄生虫病有效。它在利什曼原虫感染中的作用可能很有前途。在这篇综述中,我们提供了该疾病的重要方面、寄生虫用来抑制细胞凋亡的策略以及青蒿素在利什曼原虫感染中的作用。