Department of Parasitology, Faculty of Science, Charles University, Prague, Czechia.
National Institute of Mental Health, Klecany, Czechia.
PLoS Pathog. 2022 Feb 4;18(2):e1010302. doi: 10.1371/journal.ppat.1010302. eCollection 2022 Feb.
Helminth neuroinfections represent serious medical conditions, but the diversity of the host-parasite interplay within the nervous tissue often remains poorly understood, partially due to the lack of laboratory models. Here, we investigated the neuroinvasion of the mouse spinal cord by Trichobilharzia regenti (Schistosomatidae). Active migration of T. regenti schistosomula through the mouse spinal cord induced motor deficits in hindlimbs but did not affect the general locomotion or working memory. Histological examination of the infected spinal cord revealed eosinophilic meningomyelitis with eosinophil-rich infiltrates entrapping the schistosomula. Flow cytometry and transcriptomic analysis of the spinal cord confirmed massive activation of the host immune response. Of note, we recorded striking upregulation of the major histocompatibility complex II pathway and M2-associated markers, such as arginase or chitinase-like 3. Arginase also dominated the proteins found in the microdissected tissue from the close vicinity of the migrating schistosomula, which unselectively fed on the host nervous tissue. Next, we evaluated the pathological sequelae of T. regenti neuroinvasion. While no demyelination or blood-brain barrier alterations were noticed, our transcriptomic data revealed a remarkable disruption of neurophysiological functions not yet recorded in helminth neuroinfections. We also detected DNA fragmentation at the host-schistosomulum interface, but schistosomula antigens did not affect the viability of neurons and glial cells in vitro. Collectively, altered locomotion, significant disruption of neurophysiological functions, and strong M2 polarization were the most prominent features of T. regenti neuroinvasion, making it a promising candidate for further neuroinfection research. Indeed, understanding the diversity of pathogen-related neuroinflammatory processes is a prerequisite for developing better protective measures, treatment strategies, and diagnostic tools.
寄生虫神经感染是严重的医学病症，但由于缺乏实验室模型，宿主-寄生虫在神经组织中的相互作用的多样性仍未被充分理解。在这里，我们研究了 Regenti 血吸虫（Schistosomatidae）对小鼠脊髓的神经入侵。Regenti 血吸虫的幼体主动迁移通过小鼠脊髓导致后肢运动功能障碍，但不影响一般运动或工作记忆。受感染脊髓的组织学检查显示嗜酸性脑膜炎，嗜酸性粒细胞丰富的浸润物包围着幼体。对感染脊髓的流式细胞术和转录组分析证实了宿主免疫反应的大量激活。值得注意的是，我们记录到主要组织相容性复合体 II 途径和与 M2 相关的标记物（如精氨酸酶或几丁质酶样 3）的显著上调。精氨酸酶还主导着从迁移的幼体附近微解剖组织中发现的蛋白质，这些蛋白质无选择地摄取宿主的神经组织。接下来，我们评估了 Regenti 血吸虫神经入侵的病理后果。虽然没有发现脱髓鞘或血脑屏障改变，但我们的转录组数据显示，神经生理功能出现了显著破坏，这在寄生虫神经感染中尚未记录到。我们还在宿主-幼体界面检测到 DNA 片段化，但幼体抗原并未影响神经元和神经胶质细胞在体外的活力。总的来说，运动改变、神经生理功能的显著破坏和强烈的 M2 极化是 Regenti 血吸虫神经入侵的最显著特征，使其成为进一步神经感染研究的有前途的候选者。事实上，了解病原体相关神经炎症过程的多样性是开发更好的保护措施、治疗策略和诊断工具的前提。
