Division of Cellular, Nutritional and Physiological Sciences, Department of Human Biology, Neuroscience Institute and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Division of Cellular, Nutritional and Physiological Sciences, Department of Human Biology, Neuroscience Institute and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Int J Parasitol. 2021 Jul;51(8):685-692. doi: 10.1016/j.ijpara.2020.12.008. Epub 2021 Mar 20.
Human cysticercosis is a disease caused by larvae of the cestode Taenia solium. It is an important common cause of adult-onset seizures world-wide where it exacts a debilitating toll on the health and well-being of affected communities. It is commonly assumed that the major symptoms associated with cysticercosis are a result of the direct presence of larvae in the brain. As a result, the possible effects of peripherally located larvae on the central nervous system are not well understood. To address this question, we utilised the Taenia crassiceps intra-peritoneal murine model of cysticercosis, where larvae are restricted to the peritoneal cavity. In this model, previous research has observed behavioural changes in rodents but not the development of seizures. Here we used ELISAs, immunoblotting and the Evans Blue test for blood-brain barrier permeability to explore the central effects of peripheral infection of mice with T. crassiceps. We identified high levels of parasite-targeting immunoglobulins in the sera of T. crassiceps-infected mice. We show that the T. crassciceps larvae themselves also contain and release host immunoglobulins over time. Additionally, we describe, for the first known time, significantly increased levels of IgG within the hippocampi of infected mice, which are accompanied by changes in blood-brain barrier permeability. However, these T. crassiceps-induced changes were not accompanied by alterations to the levels of proinflammatory, pro-seizure cytokines in the hippocampus. These findings contribute to the understanding of systemic and neuroimmune responses in the T. crassiceps model of cysticercosis, with implications for the pathogenesis of human cysticercosis.
人类囊尾蚴病是一种由带绦虫幼虫引起的疾病。它是全世界导致成人癫痫的重要常见原因,对受影响社区的健康和福祉造成了严重影响。人们通常认为囊尾蚴病的主要症状是幼虫直接存在于大脑中。因此,对位于外围的幼虫对中枢神经系统的可能影响了解甚少。为了解决这个问题,我们利用了 Taenia crassiceps 腹腔内囊尾蚴病的小鼠模型,其中幼虫被限制在腹腔内。在这个模型中,先前的研究观察到了啮齿动物的行为变化,但没有观察到癫痫发作。在这里,我们使用 ELISA、免疫印迹和 Evans Blue 试验来探索外周感染 T. crassiceps 对小鼠中枢神经系统的影响。我们在 T. crassiceps 感染小鼠的血清中发现了高水平的寄生虫靶向免疫球蛋白。我们表明,T. crassciceps 幼虫本身也会随着时间的推移包含和释放宿主免疫球蛋白。此外,我们首次描述了感染小鼠海马中 IgG 水平显著增加,并伴有血脑屏障通透性的变化。然而,这些 T. crassiceps 引起的变化并没有伴随着海马中促炎、促痫细胞因子水平的改变。这些发现有助于理解 T. crassiceps 囊尾蚴病模型中的全身和神经免疫反应,对人类囊尾蚴病的发病机制有影响。