Taenialarvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling

Abstract

52Larvae of the cestodes Taenia solium and Taenia crassiceps infect the central nervous system of humans. 53Taenia solium larvae in the brain cause neurocysticercosis, the leading cause of adult-acquired epilepsy 54 worldwide. Relatively little is understood about how cestode-derived products modulate host neural and 55 immune signalling. Acetylcholinesterases, a class of enzyme that degrade acetylcholine, are produced by a 56 host of parasitic worms to aid their survival in the host. Acetylcholine is an important signalling molecule in 57 both the human nervous and immune systems, with powerful modulatory effects on the excitability of 58 cortical networks. Therefore, it is important to establish whether cestode derived acetylcholinesterases may 59 alter host neuronal cholinergic signalling. Here we make use of multiple techniques to profile 60 acetylcholinesterase activity in different extracts of both Taenia crassiceps and Taenia solium larvae. We find 61 that the larvae of both species contain substantial acetylcholinesterase activity. However, 62 acetylcholinesterase activity is lower in Taenia solium as compared to Taenia crassiceps larvae. Further, 63 whilst we observed acetylcholinesterase activity in all fractions of Taenia crassiceps larvae, including on the 64 membrane surface and in the excreted/secreted extracts, we could not identify acetylcholinesterases on the 65 membrane surface or in the excreted/secreted extracts of Taenia solium larvae. Finally, using whole-cell 66 3 patch clamp recordings in rat hippocampal brain slice cultures, we demonstrate that Taenia larval derived 67 acetylcholinesterases can modify neuronal responses to acetylcholine. Together, these findings highlight the 68 possibility that Taenia larval acetylcholinesterases can interfere with cholinergic signalling in the host, 69 potentially contributing to pathogenesis in neurocysticercosis. 70 71 Author summary 72Infection of the human nervous system with larvae of the parasite Taenia solium is a significant cause of 73 acquired epilepsy worldwide. Despite this, the precise cellular and molecular mechanisms underlying 74 epileptogenesis in neurocysticercosis remain unclear. Acetylcholinesterases are a family of enzymes widely 75 produced by helminthic parasites. These enzymes facilitate the breakdown of acetylcholine, which is also a 76 major neurotransmitter in the human nervous system. If T. solium larvae produce acetylcholinesterases, this 77 could potentially disrupt host cholinergic signalling, which may in turn contribute to seizures and epilepsy. 78We therefore set out to investigate the presence and activity of acetylcholinesterases in T. solium larvae, as 79 well as in Taenia crassiceps larvae, a species commonly used as a model parasite in neurocysticercosis 80 research. We found that both T. crassiceps and T. solium larvae produce acetylcholinesterases with 81 substantial activity. We further demonstrate that the acetylcholinesterase activity in the products of these 82 parasites is sufficient to disrupt cholinergic s...

Genome of the fatal tapeworm Sparganum proliferum uncovers mechanisms for cryptic life cycle and aberrant larval proliferation

“…Acetylcholinesterases have a well-defined role in cholinergic neurotransmission in both vertebrates and invertebrates 43 , but they are also known to be secreted by a variety of parasitic nematodes and have been speculated to work in modulating host's immunity, inflammation and physiology 44,45 . The high expression of the gene in the medusaform made us conceive a possibility that it plays a role in the parasitism in some manner, though no secretion signal peptides were identified in the protein and little is known about secreted acetylcholinesterases of cestodes 46 .…”

Epilepsy research in Africa: A scoping review by the ILAE Pediatric Commission Research Advocacy Task Force

“…Despite the public health awareness of the spread of cysticercosis, much remains unknown about many key pathogenic aspects of the disease, including how cerebral infection with T solium results in the development of seizures 63 . Eloquent basic science research suggests that Taenia larval acetylcholinesterases can interfere with cholinergic signaling in the host, potentially contributing to pathogenesis in neurocysticercosis 64 …”

“…63 Eloquent basic science research suggests that Taenia larval acetylcholinesterases can interfere with cholinergic signaling in the host, potentially contributing to pathogenesis in neurocysticercosis. 64…”