Abstract
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.
Highlights
Parasitic helminths often invade the central nervous system (CNS) of mammals, including humans
Our study deeply characterized the neuroinvasion of the mouse spinal cord by the neuropathogenic flatworm Trichobilharzia regenti
Its behavior within the nervous tissue and clinical outcome of the infection resemble those observed in human diseases
Summary
Parasitic helminths often invade the central nervous system (CNS) of mammals, including humans. The clinical manifestation of helminth neuroinfections ranges from mostly asymptomatic to very severe, leading to sensory or cognitive deficits and seizures or epilepsy [2,3,4]. Many factors, such as parasite burden or localization within the CNS, influence the course and outcome of the neuroinfection [5]. The host immune response affects helminth growth and survival but might participate in the pathogenesis or behavioral alterations [6,7]. A deep understanding of host-parasite immune interactions is required to develop better protective measures, treatment strategies, and diagnostic tools
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