Silva Pereira Sara, Brás Daniela, Porqueddu Teresa, Nascimento Ana M, De Niz Mariana
Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Católica Biomedical Research Centre, Católica Medical School, Universidade Católica Portuguesa, Lisbon, Portugal.
Cell Surf. 2023 Oct 27;10:100113. doi: 10.1016/j.tcsw.2023.100113. eCollection 2023 Dec 15.
Multiple blood-borne pathogens infecting mammals establish close interactions with the host vascular endothelium as part of their life cycles. In this work, we investigate differences in the interactions of three species: and with the blood vasculature. Infection with these species results in vastly different pathologies, including different effects on vascular homeostasis, such as changes in vascular permeability and microhemorrhages. While all three species are extracellular parasites, is strictly intravascular, while is capable of surviving both extra- and intravascularly. Our knowledge regarding tropism and its capacity of migration across the vascular endothelium is unknown. In this work, we show for the first time that parasites sequester to the vascular endothelium of most organs, and that, like Y486 is largely incapable of extravasation. Infection with this parasite species results in a unique effect on vascular endothelium receptors including general downregulation of ICAM1 and ESAM, and upregulation of VCAM1, CD36 and E-selectin. Our findings on the differences between the two sequestering species ( and ) and the non-sequestering, but extravasating, raise important questions on the relevance of sequestration to the parasite's survival in the mammalian host, and the evolutionary relevance of both sequestration and extravasation.
多种感染哺乳动物的血源性病原体在其生命周期中与宿主血管内皮建立密切相互作用。在这项研究中,我们调查了三种物种(此处原文缺失物种名称)与血管系统相互作用的差异。感染这些物种会导致截然不同的病理状况,包括对血管稳态的不同影响,如血管通透性变化和微出血。虽然这三种物种都是细胞外寄生虫,但(此处原文缺失物种名称)严格存在于血管内,而(此处原文缺失物种名称)能够在血管内外存活。我们对(此处原文缺失物种名称)的嗜性及其穿越血管内皮的迁移能力尚不清楚。在这项研究中,我们首次表明(此处原文缺失物种名称)寄生虫会在大多数器官的血管内皮中滞留,并且与(此处原文缺失物种名称)Y486一样,基本上无法渗出血管。感染这种寄生虫物种会对血管内皮受体产生独特影响,包括细胞间黏附分子1(ICAM1)和内皮细胞选择素黏附分子(ESAM)普遍下调,以及血管细胞黏附分子1(VCAM1)、血小板糖蛋白CD36和E选择素上调。我们对两种滞留物种(此处原文缺失物种名称)和非滞留但可渗出血管的(此处原文缺失物种名称)之间差异的研究结果,引发了关于滞留与寄生虫在哺乳动物宿主中生存相关性以及滞留和渗出的进化相关性的重要问题。