Department of Morphology, Federal University of Minas Gerais, Brazil.
Curr Top Membr. 2019;84:217-238. doi: 10.1016/bs.ctm.2019.08.002. Epub 2019 Sep 4.
Intracellular pathogens depend on specific mechanisms to be able to gain entry and survive into their host cells. For this, they subvert pathways involved in physiological cellular processes. Here we are going to focus on how two protozoan parasites, Trypanosoma cruzi and Leishmania sp, which may cause severe diseases in humans, use plasma membrane repair (PMR) mechanisms to gain entry in host intracellular environment. T. cruzi is the causative agent of Chagas disease, a disease originally endemic of central and South America, but that has become widespread around the globe. T. cruzi is able to invade any nucleated cell, but muscle cells are usually the main targets during chronic disease. During host cell contact, the parasite interacts with proteins at the host cell surface and may cause damage to their membrane, which has been shown to be responsible for inducing intracellular calcium increase and PMR-related events that culminate with parasite internalization. The same was recently observed for Leishmania sp, when infecting nonprofessional phagocytic cells, such as fibroblasts. Other pathogens, such as viruses or bacteria may also use PMR-related events for invasion and vacuole escape/maturation. In some cases, PMR may also be responsible to modulate pathogen intracellular development. These other PMR roles in pathogen infections will also be briefly discussed.
细胞内病原体依赖于特定的机制才能进入并在宿主细胞中存活。为此,它们颠覆了涉及生理细胞过程的途径。在这里,我们将重点关注两种原生动物寄生虫,即克氏锥虫和利什曼原虫,它们可能会导致人类患上严重疾病,它们如何利用质膜修复(PMR)机制进入宿主细胞内环境。克氏锥虫是恰加斯病的病原体,这种疾病最初流行于中美洲和南美洲,但现已在全球范围内广泛传播。克氏锥虫能够入侵任何有核细胞,但在慢性疾病期间,肌肉细胞通常是主要靶标。在与宿主细胞接触时,寄生虫与宿主细胞表面的蛋白质相互作用,可能会导致其膜受损,这已被证明是导致细胞内钙增加和与 PMR 相关的事件的原因,这些事件最终导致寄生虫内化。最近在感染非专业吞噬细胞(如成纤维细胞)时也观察到了同样的情况。其他病原体,如病毒或细菌,也可能利用与 PMR 相关的事件进行入侵和空泡逃逸/成熟。在某些情况下,PMR 也可能负责调节病原体的细胞内发育。这些其他 PMR 在病原体感染中的作用也将简要讨论。