Cunningham Anna C
Department of Pathology, The University of Tennessee, Memphis, Tennessee 38163, USA.
Exp Mol Pathol. 2002 Apr;72(2):132-41. doi: 10.1006/exmp.2002.2418.
Leishmania are a resilient group of intracellular parasites that infect macrophages. The resultant complex of diseases, or leishmaniases, caused by the parasites affect over twelve million people worldwide. Leishmania have developed unique adaptive mechanisms to ensure their survival in the harsh environments faced throughout their life cycle. These parasites must not only contend with the hostile digestive conditions found within the sand fly vector, but they must also avoid destruction by the host immune system while in the bloodstream, before entering the macrophage. To do so, Leishmania express unique lipophosphoglycan (LPG) molecules and the metalloprotease gp63, among other proteins, on their cell surface. To enter the macrophage, Leishmania utilizes a variety of cellular receptors to mediate endocytosis. Once inside the macrophage, Leishmania is protected from phagolysosome degradation by a variety of adaptations to inhibit cellular defense mechanisms. These include the inhibition of phagosome-endosome fusion, hydrolytic enzymes, cell signaling pathways, nitric oxide production, and cytokine production. While other parasites can also infect macrophages, Leishmania is distinctive in that it not only relies on its own defenses to survive and reproduce within the macrophage phagolysosome, but Leishmania also manipulates the host immune response in order to protect itself and to gain entry into the cell. These unique adaptive mechanisms help promote Leishmania survival.
利什曼原虫是一类能感染巨噬细胞的具有韧性的细胞内寄生虫。由这些寄生虫引起的一系列复杂疾病，即利什曼病，在全球影响着超过1200万人。利什曼原虫已经进化出独特的适应机制，以确保它们在整个生命周期所面临的恶劣环境中生存。这些寄生虫不仅要应对在白蛉媒介体内发现的恶劣消化环境，而且在进入巨噬细胞之前，它们还必须在血液中避免被宿主免疫系统破坏。为此，利什曼原虫在其细胞表面表达独特的脂磷壁酸（LPG）分子和金属蛋白酶gp63等蛋白质。为了进入巨噬细胞，利什曼原虫利用多种细胞受体介导内吞作用。一旦进入巨噬细胞，利什曼原虫通过多种适应性变化来抑制细胞防御机制，从而免受吞噬溶酶体的降解。这些适应性变化包括抑制吞噬体 - 内体融合、水解酶、细胞信号通路、一氧化氮生成和细胞因子生成。虽然其他寄生虫也能感染巨噬细胞，但利什曼原虫的独特之处在于，它不仅依靠自身的防御机制在巨噬细胞吞噬溶酶体内生存和繁殖，而且还操纵宿主免疫反应以保护自身并进入细胞。这些独特的适应机制有助于促进利什曼原虫的生存。
