Division of Cell Biology, Department of Human Biology and Neuroscience Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Institute for Medical Microbiology, Immunology and Hygiene, Centre for Global Health, Technical University Munich (TUM), Munich, Germany.
PLoS Negl Trop Dis. 2020 Dec 21;14(12):e0008966. doi: 10.1371/journal.pntd.0008966. eCollection 2020 Dec.
Larvae of the cestodes Taenia solium and Taenia crassiceps infect the central nervous system of humans. Taenia solium larvae in the brain cause neurocysticercosis, the leading cause of adult-acquired epilepsy worldwide. Relatively little is understood about how cestode-derived products modulate host neural and immune signalling. Acetylcholinesterases, a class of enzyme that breaks down acetylcholine, are produced by a host of parasitic worms to aid their survival in the host. Acetylcholine is an important signalling molecule in both the human nervous and immune systems, with powerful modulatory effects on the excitability of cortical networks. Therefore, it is important to establish whether cestode derived acetylcholinesterases may alter host neuronal cholinergic signalling. Here we make use of multiple techniques to profile acetylcholinesterase activity in different extracts of both Taenia crassiceps and Taenia solium larvae. We find that the larvae of both species contain substantial acetylcholinesterase activity. However, acetylcholinesterase activity is lower in Taenia solium as compared to Taenia crassiceps larvae. Further, whilst we observed acetylcholinesterase activity in all fractions of Taenia crassiceps larvae, including on the membrane surface and in the excreted/secreted extracts, we could not identify acetylcholinesterases on the membrane surface or in the excreted/secreted extracts of Taenia solium larvae. Bioinformatic analysis revealed conservation of the functional protein domains in the Taenia solium acetylcholinesterases, when compared to the homologous human sequence. Finally, using whole-cell patch clamp recordings in rat hippocampal brain slice cultures, we demonstrate that Taenia larval derived acetylcholinesterases can break down acetylcholine at a concentration which induces changes in neuronal signalling. Together, these findings highlight the possibility that Taenia larval acetylcholinesterases can interfere with cholinergic signalling in the host, potentially contributing to pathogenesis in neurocysticercosis.
猪带绦虫和多头绦虫的幼虫感染人类中枢神经系统。猪带绦虫幼虫在大脑中引起囊虫病，是全世界成年人获得性癫痫的主要原因。相对而言，人们对绦虫衍生产物如何调节宿主神经和免疫信号知之甚少。乙酰胆碱酯酶是一类分解乙酰胆碱的酶，许多寄生虫都会产生这种酶，以帮助它们在宿主中生存。乙酰胆碱是人类神经系统和免疫系统中一种重要的信号分子，对皮质网络的兴奋性有强大的调节作用。因此，确定绦虫衍生的乙酰胆碱酯酶是否可能改变宿主神经元的胆碱能信号是很重要的。在这里，我们利用多种技术来分析多头绦虫和猪带绦虫幼虫不同提取物中的乙酰胆碱酯酶活性。我们发现两种幼虫都含有大量的乙酰胆碱酯酶活性。然而，猪带绦虫幼虫中的乙酰胆碱酯酶活性比多头绦虫幼虫低。此外，虽然我们在多头绦虫幼虫的所有馏分中都观察到了乙酰胆碱酯酶活性，包括在膜表面和排泄/分泌提取物中，但我们无法在猪带绦虫幼虫的膜表面或排泄/分泌提取物中鉴定出乙酰胆碱酯酶。生物信息学分析表明，与同源的人类序列相比，猪带绦虫乙酰胆碱酯酶具有保守的功能蛋白结构域。最后，我们在大鼠海马脑片培养物中进行全细胞膜片钳记录，证明了猪带绦虫幼虫衍生的乙酰胆碱酯酶可以在诱导神经元信号改变的浓度下分解乙酰胆碱。综上所述，这些发现强调了猪带绦虫幼虫乙酰胆碱酯酶可能干扰宿主胆碱能信号的可能性，这可能有助于囊虫病的发病机制。
