Transcriptomic analysis of subarachnoid cysts of Taenia solium reveals mechanisms for uncontrolled proliferation and adaptations to the microenvironment

Subarachnoid neurocysticercosis (SANCC) is caused by an abnormally transformed form of the metacestode or larval form of the tapewormTaenia solium. In contrast to vesicular parenchymal and ventricular located cysts that contain a viable scolex and are anlage of the adult tapeworm, the subarachnoid cyst proliferates to form aberrant membranous cystic masses within the subarachnoid spaces that cause mass effects and acute and chronic arachnoiditis. How subarachnoid cyst proliferates and interacts with the human host is poorly understood, but parasite stem cells (germinative cells) likely participate. RNA-seq analysis of the subarachnoid cyst bladder wall compared to the bladder wall and scolex of the vesicular cyst revealed that the subarachnoid form exhibits activation of signaling pathways that promote proliferation and increased lipid metabolism. These adaptions allow growth in a nutrient-limited cerebral spinal fluid. In addition, we identified therapeutic drug targets that would inhibit growth of the parasite, potentially increase effectiveness of treatment, and shorten its duration. Gene expression was calculated for three replicates of racemose cysts, vesicular cycts and scolex. This was followed by differential gene expression analysis.

蛛网膜下腔型神经囊尾蚴病（Subarachnoid neurocysticercosis, SANCC）由猪肉绦虫（Taenia solium）的中绦期（囊尾蚴）异常增殖形态引发。与内含活性头节、可发育为成虫的脑实质及脑室囊状囊肿不同，蛛网膜下腔囊肿会在蛛网膜下腔内增殖形成异常膜性囊块，引发占位效应与急慢性蛛网膜炎。目前关于蛛网膜下腔囊肿的增殖机制及其与人类宿主的互作模式尚不明晰，但寄生虫干细胞（生发细胞，germinative cells）极可能参与这一过程。相较于囊状囊肿的囊壁与头节，本研究对蛛网膜下腔囊肿囊壁开展RNA测序（RNA-seq）分析后发现，蛛网膜下腔型虫体激活了促进增殖与增强脂质代谢的信号通路。此类适应性改变使其可在营养受限的脑脊液环境中存活增殖。此外，本研究还筛选出可抑制该寄生虫生长的潜在治疗靶点，有望提升治疗效果并缩短疗程。本研究对葡萄状囊尾蚴、囊状囊肿及头节各设置3次生物学重复以计算基因表达量，随后开展差异基因表达分析。